Total synthesis of prostaglandin j natural products by tereoretentive metathesis

ABSTRACT

This invention relates generally to the synthesis of Δ12-Prostaglandin J product using stereoretentive ruthenium olefin metathesis catalysts supported by dithiolate ligands. Δ12-Prostaglandin J products were generated with excellent selectivity (&gt;99% Z) and in moderate to high/good yields (47% to 80% yield; 58% to 80% yield).

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 62/671,891 filed May 15, 2018, and of U.S. ProvisionalPatent Application No. 62/803,603 filed Feb. 11, 2019, the contents ofwhich are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under NIH Grant No.GM031332. The U.S. Government has certain rights in the invention.

TECHNICAL FIELD

Prostaglandins are an important class of naturally occurring moleculesthat are found in mammalian tissues and exhibit a broad range ofbiological functions and widespread medical applications. [Marks F. andFürstenberger G. Prostagandins, Laukotrienes and Other Eicosanoids;Wiley-Blackwell, 1999. Funk, C. D. Prostaglandins and Leukotrienes:Advances in Eicosanoid Biology. Science 2001, 294, 1871-1875.]

Efforts directed toward the synthesis of various prostaglandins has hada profound effect on the development of new strategies and tacticsemployed in the field of synthetic chemistry, emanating from the seminalstudies of Corey beginning in the 1960's. [Corey, E. J.; Weinshenker, N.M.; Schaaf, T. K.; Huber, W. Stereo-Controlled Synthesis ofDI-Prostaglandins F2.alpha, and E2. J. Am. Chem. Soc. 1969, 91,5675-5677. Das, S.; Chandrasekhar, S.; Yadav, J. S.; Grée, R. RecentDevelopments in the Synthesis of Prostaglandins and Analogues. Chem.Rev. 2007, 107, 3286-3337. Peng, H.; Chen, F.-E. Recent Advances inAsymmetric Total Synthesis of Prostaglandins. Org. Biomol. Chem. 2017,15, 6281-6301.]

BACKGROUND

The recently discovered Δ¹²-prostaglandin J family (1), (2), (3) and (4)as shown in FIG. 1, features a unique cross-conjugated dienone motif andappealing anticancer activity. [Straus D. S.; Glass C. K. CyclopentenoneProstaglandins: New Insights on Biological Activities and CellularTargets. Med. Res. Rev. 2001, 21, 185-210.]

Δ¹²-PGJ₃ (3), for example, was isolated as a secondary metabolite andwas shown to selectively induce apoptosis of leukemia stem cells overnormal hematopoietic stems cells with high potency. [Hegde, S.; Kaushal.N.; Ravindra K. C.; Chiaro, C.; Hafer, K. T.; Gandhi, U. H.; Thompson,J. T.; van den Heuvel, J. P.; Kennett, M. J.; Hankey, P.; Paulson R. F.;Prabhu K. S. Δ¹²-Prostaglandin J₃, an Omega-3 Fatty Acid-DerivedMetabolite, Selectively Ablates Leukemia Stem Cells in Mice. Blood 2011,118, 6909-6919.]

Studies of its stability, bioavailability, and hypersensitivity makeΔ¹²-PGJ₃ an intriguing drug candidate for leukemia treatment. [Kudva, A.K.; Kaushal, N.; Mohinta, S.; Kennett, M. J.; August, A.; Paulson, R.F.; Prabhu, K. S. Evaluation of the Stability, Bioavailability, andHypersensitivity of the Omega-3 Derived Anti-Leukemic Prostaglandin:Δ¹²-Prostaglandin J₃ PLOS ONE 2013, 8, e80622.]

Synthetic efforts toward Δ¹²-prostaglandin J compounds began in 2003,with a number of syntheses of Δ¹²-PGJ₂ (1) and 15d-PGJ₂ (2) reportedthrough various approaches. [Bickley, J. F.; Jadhav, V.; Roberts, S. M.;Santoro, M. G.; Steiner, A.; Sutton, P. W. Synthesis of Optically ActiveProstaglandin J₂ and 15-Deoxy-Δ^(12,14) Prostaglandin J₂ . Synlett 2003,1170-1174. Brummond, K. M.; Sill, P. C.; Chen, H. The First TotalSynthesis of 15-Deoxy-Δ^(12,14)-Prostaglandin J₂ and the UnambiguousAssignment of the C14 Stereochemistry. Org. Lett. 2004, 6, 149-152.Acharya, H. P.; Kobayashi, Y. Total Synthesis of Δ¹²-PGJ₂,15-Deoxy-Δ^(12,14)-PGJ₂, and Related Compounds. Tetrahedron Lett. 2004,45, 1199-1202. Acharya, H. P.; Kobayashi, Y. Highly Efficient TotalSynthesis of Δ¹²-PGJ₂, 15-Deoxy-Δ^(12,14)-PGJ₂, and Their Analogues.Tetrahedron 2006, 62, 3329-3343. Kim, N.-J.; Moon, H.; Park. T.; Yun,H.; Jung, J.-W.; Chang, D.-J.; Kim, D.-D.; Suh, Y.-G. Concise andEnantioselective Total Synthesis of 15-Deoxy-Δ^(12,14)-Prostaglandin J₂J. Org. Chem. 2010, 75, 7458-7460. Egger, J.; Fischer, S.; Bretscher,P.; Freigang, S.; Kopf, M.; Carreira, E. M. Total Synthesis ofProstaglandin 15d-PGJ₂ and Investigation of Its Effect on the Secretionof IL-6 and IL-12. Org. Lett. 2015, 17, 4340-4343.]

Elegant contributions to the total synthesis of Δ¹²-PGJ₃. (3) werereported by Nicolaou and co-workers and more recently by the Aggarwalgroup. [Nicolaou, K. C.; Heretsch, P.; El Marrouni, A.; Hale, C. R. H.;Pulukuri, K. K.; Kudva, A. K.; Narayan, V.; Prabhu, K. S. TotalSynthesis of Δ¹²-Prostaglandin J, a Highly Potent and SelectiveAntileukemic Agent. Angew. Chem. Int. Ed. 2014, 53, 10443-10447.Nicolaou, K. C.; Pulukuri, K. K.; Yu, R.; Rigol, S.; Heretsch, P.;Grove, C. I.; Hale, C. R. H.; El Marrouni, A. Total Synthesis of Δ¹²Prostaglandin J₃; Evolution of Synthetic Strategies to a StreamlinedProcess. Chem.-Eur. J. 2016, 22, 8559-8570. Petšs, A.; Gandhamsetty, N.;Smith, J. R.; Mailhol, D.; Silvi, M.; Watson, A. J. A.; Perez-Powell,I.; Prévost, S.; Schützenmeister, N.; Moore, P. R.; Aggarwal V. K.Reoptimization of the Organocatalyzed Double Aldol Domino Process to aKey Enal Intermediate and Its Application to the Total Synthesis ofΔ¹²-Prostaglandin J₃ Chem.-Eur. J. 2018, 24, 9542-9545.]

A number of Δ¹²-PGJ₃ analogues were also accessible via a streamlinedsynthesis developed by Nicolaou and co-workers to enable a comprehensivestructural-activity relationship (SAR) study of their anti-canceractivities. [Nicolaou, K. C.; Pulukuri, K. K.; Rigol, S.; Heretsch, P.;Yu, R.; Grove, C. I.; Hale, C. R. H.; ElMarrouni, A.; Fetz, V.;Bronstrup, M.; Aujay M.; Sandoval J.; Gavrilyuk J. Synthesis andBiological Investigation of Δ¹²-Prostaglandin J₃ (Δ¹²-PGJ₃) Analoguesand Related Compounds. J. Am. Chem. Soc. 2016, 138, 6550-6560.]

DETAILED DESCRIPTION Terminology and Definitions

Unless otherwise indicated, the invention is not limited to specificreactants, reaction conditions, or the like, as such may vary. It isalso to be understood that the terminology used herein is for thepurpose of describing particular embodiments and is not to beinterpreted as being limiting.

As used in the specification and the appended claims, the singular forms“a,” “an,” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a substituent”encompasses a single substituent as well as two or more substituents,and the like.

As used in the specification and the appended claims, the terms “forexample”. “for instance”, “such as” or “including” are meant tointroduce examples that further clarify more general subject matter.Unless otherwise specified, these examples are provided only as an aidfor understanding the invention and are not meant to be limiting in anyfashion.

In this specification and in the claims that follow, reference will bemade to a number of terms, which shall be defined to have the meaningsas described herein.

The term “alkyl” as used herein, refers to a linear, branched, or cyclicsaturated hydrocarbon group typically although not necessarilycontaining 1 to 24 carbon atoms, preferably 1 to 12 carbon atoms, suchas methyl (Me), ethyl (Et), n-propyl (Pr or n-Pr), isopropyl (i-Pr),n-butyl (Bu or n-Bu), isobutyl (i-Bu), t-butyl (t-Bu), octyl (Oct),decyl, and the like, as well as cycloalkyl groups such as cyclopentyl(Cp), cyclohexyl (Cy) and the like. Generally, although again notnecessarily, alkyl groups herein contain 1 to about 8 carbon atoms. Theterm “lower alkyl” refers to an alkyl group of 1 to 6 carbon atoms, andthe specific term “cycloalkyl” refers to a cyclic alkyl group, typicallyhaving 3 to 8, preferably 5 to 7, carbon atoms. The term “substitutedalkyl” refers to alkyl substituted with one or more substituent groups,and the terms “heteroatom-containing alkyl” and “heteroalkyl” refer toalkyl in which at least one carbon atom is replaced with a heteroatom.If not otherwise indicated, the terms “alkyl” and “lower alkyl” includelinear, branched, cyclic, unsubstituted, substituted, and/orheteroatom-containing alkyl and lower alkyl, respectively.

The term “alkylene” as used herein refers to a difunctional linear,branched, or cyclic alkyl group, where “alkyl” is as defined above.

The term “alkenyl” as used herein refers to a linear, branched, orcyclic hydrocarbon group of 2 to 24 carbon atoms containing at least onedouble bond, such as ethenyl, n-propenyl, iso-propenyl, n-butenyl,iso-butenyl, octenyl, decenyl, tetradecenyl, hexadecenyl, and the like.Preferred alkenyl groups herein contain 2 to 12 carbon atoms. The term“lower alkenyl” refers to an alkenyl group of 2 to 6 carbon atoms, andthe specific term “cycloalkenyl” refers to a cyclic alkenyl group,preferably having 3 to g carbon atoms. The term “substituted alkenyl”refers to alkenyl substituted with one or more substituent groups, andthe terms “heteroatom-containing alkenyl” and “heteroalkenyl” refer toalkenyl in which at least one carbon atom is replaced with a heteroatom.If not otherwise indicated, the terms “alkenyl” and “lower alkenyl”include linear, branched, cyclic, unsubstituted, substituted, and/orheteroatom-containing alkenyl and lower alkenyl, respectively.

The term “alkenylene” as used herein refers to a difunctional linear,branched, or cyclic alkenyl group, where “alkenyl” is as defined above.

The term “alkynyl” as used herein refers to a linear or branchedhydrocarbon group of 2 to 24 carbon atoms containing at least one triplebond, such as ethynyl, n-propynyl, and the like. Preferred alkynylgroups herein contain 2 to 12 carbon atoms. The term “lower alkynyl”refers to an alkynyl group of 2 to 6 carbon atoms. The term “substitutedalkynyl” refers to alkynyl substituted with one or more substituentgroups, and the terms “heteroatom-containing alkynyl” and“heteroalkynyl” refer to alkynyl in which at least one carbon atom isreplaced with a heteroatom. If not otherwise indicated, the terms“alkynyl” and “lower alkynyl” include linear, branched, unsubstituted,substituted, and/or heteroatom-containing alkynyl and lower alkynyl,respectively.

The term “alkynylene” as used herein refers to a difunctional alkynylgroup, where “alkynyl” is as defined above.

The term “alkoxy” as used herein refers to an alkyl group bound througha single, terminal ether linkage; that is, an “alkoxy” group may berepresented as —O-alkyl where alkyl is as defined above. A “loweralkoxy” group refers to an alkoxy group containing 1 to 6 carbon atoms.Analogously, “alkenyloxy” and “lower alkenyloxy” respectively refer toan alkenyl and lower alkenyl group bound through a single, terminalether linkage, and “alkynyloxy” and “lower alkynyloxy” respectivelyrefer to an alkynyl and lower alkynyl group bound through a single,terminal ether linkage.

The term “aryl” as used herein, and unless otherwise specified, refersto an aromatic substituent containing a single aromatic ring or multiplearomatic rings that are fused together, directly linked, or indirectlylinked (such that the different aromatic rings are bound to a commongroup such as a methylene or ethylene moiety). Preferred aryl groupscontain 5 to 24 carbon atoms, and particularly preferred aryl groupscontain 6 to 10 carbon atoms. Exemplary aryl groups contain one aromaticring or two fused or linked aromatic rings, e.g., phenyl (Ph), naphthyl,biphenyl, diphenylether, diphenylamine, benzophenone, phenanthryl andthe like. “Substituted aryl” refers to an aryl moiety substituted withone or more substituent groups, and the terms “heteroatom containingaryl” and “heteroaryl” refer to aryl substituents in which at least onecarbon atom is replaced with a heteroatom, as will be described infurther detail herein.

The term “aryloxy” as used herein refers to an aryl group bound througha single, terminal ether linkage, wherein “aryl” is as defined above. An“aryloxy” group may be represented as —O-aryl where aryl is as definedabove. Preferred aryloxy groups contain 5 to 24 carbon atoms, andparticularly preferred aryloxy groups contain 6 to 10 carbon atoms.Examples of aryloxy groups include, without limitation, phenoxy,o-halo-phenoxy, m-halo-phenoxy, p-halo-phenoxy, o-methoxy-phenoxy,m-methoxy-phenoxy, p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy,3,4,5-trimethoxy-phenoxy, and the like.

The term “alkaryl” refers to an aryl group with an alkyl substituent,and the term “aralkyl” refers to an alkyl group with an arylsubstituent, wherein “aryl” and “alkyl” are as defined above. Preferredalkaryl and aralkyl groups contain 6 to 24 carbon atoms, andparticularly preferred alkaryl and aralkyl groups contain 6 to 16 carbonatoms. Alkaryl groups include, without limitation, p-methylphenyl,2,4-dimethylphenyl, p-cyclohexylphenyl, 2,7-dimethylnaphthyl,7-cyclooctylnaphthyl, 3-ethyl-cyclopenta-1,4-diene, and the like.Examples of aralkyl groups include, without limitation, benzyl,2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl.4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl,4-benzylcyclohexylmethyl, and the like. The terms “alkaryloxy” and“aralkyloxy” refer to substituents of the formula —OR wherein R isalkaryl or aralkyl, respectively, as just defined.

The term “acyl” refers to substituents having the formula —(CO)-alkyl,—(CO)-aryl, —(CO)-aralkyl, —(CO)-alkaryl, —(CO)-alkenyl, or—(CO)-alkynyl, and the term “acyloxy” refers to substituents having theformula —O(CO)-alkyl, —O(CO)-aryl, —O(CO)-aralkyl, —O(CO)-alkaryl,—O(CO)-alkenyl, or —(CO)-alkynyl wherein “alkyl,” “aryl”, “aralkyl”,“alkaryl”, “alkenyl”, and “alkynyl” are as defined above. The acetoxygroup (—O(CO)CH₃, often abbreviated as —OAc) is a common example of anacyloxy group.

The terms “cyclic” and “ring” refer to alicyclic or aromatic groups thatmay or may not be substituted and/or heteroatom containing, and that maybe monocyclic, bicyclic, or polycyclic. The term “alicyclic” is used inthe conventional sense to refer to an aliphatic cyclic moiety, asopposed to an aromatic cyclic moiety, and may be monocyclic, bicyclic orpolycyclic.

The term “polycyclic ring” refers to alicyclic or aromatic groups thatmay or may not be substituted and/or heteroatom containing, and thathave at least two closed rings tethered, fused, linked via a single bondor bridged. Polycyclic rings include without limitation naphthyl,biphenyl, phenanthryl and the like.

The term “spiro compound” refers to a chemical compound, that presents atwisted structure of two or more rings (a ring system), in which 2 or 3rings are linked together by one common atom,

The terms “halo” and “halogen” and “halide” are used in the conventionalsense to refer to a fluorine (F), chlorine (Cl), bromine (Br), or iodine(I) substituent.

The terms “cis”/“2” and “trans”/“E” as used herein, are usedinterchangeably and refer to the geometry of the double bonds.

“Hydrocarbyl” refers to univalent hydrocarbyl radicals containing 1 to24 carbon atoms, most preferably 1 to 12 carbon atoms, including linear,branched, cyclic, saturated and unsaturated species, such as alkylgroups, alkenyl groups, alkynyl groups, aryl groups, and the like. Theterm “lower hydrocarbyl” refers to a hydrocarbyl group of 1 to 6 carbonatoms, preferably 1 to 4 carbon atoms, and the term “hydrocarbylene”refers to a divalent hydrocarbyl moiety containing 1 to 24 carbon atoms,preferably 1 to 12 carbon atoms, including linear, branched, cyclic,saturated and unsaturated species. The term “lower hydrocarbylene”refers to a hydrocarbylene group of 1 to 6 carbon atoms. “Substitutedhydrocarbyl” refers to hydrocarbyl substituted with one or moresubstituent groups, and the terms “heteroatom-containing hydrocarbyl”and “heterohydrocarbyl” refer to hydrocarbyl in which at least onecarbon atom is replaced with a heteroatom. Similarly, “substitutedhydrocarbylene” refers to hydrocarbylene substituted with one or moresubstituent groups, and the terms “heteroatom-containing hydrocarbylene”and “heterohydrocarbylene” refer to hydrocarbylene in which at least onecarbon atom is replaced with a heteroatom. Unless otherwise indicated,the term “hydrocarbyl” and “hydrocarbylene” are to be interpreted asincluding substituted and/or heteroatom-containing hydrocarbyl andhydrocarbylene moieties, respectively.

The term “heteroatom-containing” as in a “heteroatom-containinghydrocarbyl group” refers to a hydrocarbon molecule or a hydrocarbylmolecular fragment in which one or more carbon atoms is replaced with anatom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus orsilicon, typically nitrogen, oxygen or sulfur. Similarly, the term“heteroalkyl” refers to an alkyl substituent that isheteroatom-containing, the term “heterocyclic” refers to a cyclicsubstituent that is heteroatom-containing, the terms “heteroaryl” and“heteroaromatic” respectively refer to “aryl” and “aromatic”substituents that are heteroatom-containing, and the like. It should benoted that a “heterocyclic” group or compound may or may not bearomatic, and further that “heterocycles” may be monocyclic, bicyclic,or polycyclic as described above with respect the term “aryl.” Examplesof heteroalkyl groups include without limitation alkoxyaryl,alkylsulfanyl-substituted alkyl, N-alkylated amino alkyl, and the like.Examples of heteroaryl substituents include without limitation pyrrolyl,pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl, imidazolyl,1,2,4-triazolyl, tetrazolyl, etc., and examples of heteroatom-containingalicyclic groups include without limitation pyrrolidino, morpholino,piperazino, piperidino, etc.

By “substituted” as in “substituted hydrocarbyl”, “substituted alkyl”,“substituted aryl”, and the like, as alluded to in some of theaforementioned definitions, is meant that in the hydrocarbyl, alkyl,aryl, or other moiety, at least one hydrogen atom bound to a carbon (orother) atom is replaced with one or more non-hydrogen substituents.Examples of such substituents include, without limitation groups such ashalo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₂-C₂₄ alkenyloxy. C₂-C₂₄alkynyloxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl(including C₂-C₂₄ alkylcarbonyl (—CO-alkyl) and C₆-C₂₄ arylcarbonyl(—CO-aryl)), acyloxy (—O-acyl, including C₂-C₂₄ alkylcarbonyloxy(—O—CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (—O—CO-aryl)), C₂-C₂₄alkoxycarbonyl (—(CO)—O-alkyl), C₆-C₂₄ aryloxycarbonyl (—(CO)—O-aryl),halocarbonyl (—CO)—X where X is halo), C₂-C₂₄ alkylcarbonato(—O—(CO)—O-alkyl), C₆-C₂₄ arylcarbonato (—O—(CO)—O-aryl), carboxy(—COOH), carbamoyl (—(CO)—NH₂), mono-(C₁-C₂₄ alkyl)-substitutedcarbamoyl (—(CO)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substitutedcarbamoyl (—(CO)—N(C₅-C₂₄ alkyl)₂), mono-(C₁-C₂₄ haloalkyl)-substitutedcarbamoyl (—(CO)—NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄haloalkyl)-substituted carbamoyl (—(CO)—N(C₁-C₂₄ haloalkyl)₂),mono-(C₅-C₂₄ aryl)-substituted carbamoyl (—(CO)—NH-aryl), di-(C₅-C₂₄aryl)-substituted carbamoyl (—(CO)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄alkyl), N—(C₅-C₂₄ aryl)-substituted carbamoyl (—(CO)—N(C₁-C₂₄alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (—(CS)—NH₂), mono-(C₁-C₂₄alkyl)-substituted thiocarbamoyl (—(CS)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄alkyl)-substituted thiocarbamoyl (—(CS)—N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄aryl)-substituted thiocarbamoyl (—(CS)—NH-aryl), di-(C₅-C₂₄aryl)-substituted thiocarbamoyl (—(CS)—N(C₅-C₂₄ aryl)₂), di-N—(C₅-C₂₄alkyl), N—(C₅-C₂₄ aryl)-substituted thiocarbamoyl (—(CS)—N(C₁-C₂₄alkyl)(C₅-C₂₄ aryl), carbamido (—NH—(CO)—NH₂), cyano(—C≡N), cyanato(—O—C≡N), thiocyanato (—S—C≡N), isocyanate (—NCO), thioisocyanate(—NCS), formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH₂),mono-(C₁-C₂₄ alkyl)-substituted amino (—NH(C₁-C₂₄ alkyl), di-(C₁-C₂₄alkyl)-substituted amino ((—N(C₁-C₄ alkyl)₂), mono-(C₅-C₂₄aryl)-substituted amino (—NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substitutedamino (—N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (—NH—(CO)-alkyl), C₆-C₂₄arylamido (—NH—(CO)-aryl), imino (—CRNH where, R includes withoutlimitation H, C₁-C₂ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl,etc.), C₂-C₂₀ alkylimino (—CRN(alky), where R includes withoutlimitation H, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl,etc.), arylimino (—CRN(aryl), where R includes without limitation H,C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), nitro(—NO₂), nitroso (—NO), sulfo (—SO₂—OH), C₁-C₂₄ alkylsulfanyl (—S-alkyl;also termed “alkylthio”), C₅-C₂₄ arylsulfanyl (—S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (—(SO)-alkyl), C₅-C₂₄ arylsulfinyl(—(SO)-aryl), C₁-C₂₄ alkylsulfonyl (—SO₂-alkyl), C₁-C₂₄monoalkylaminosulfonyl (—SO₂—N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl(—SO₂—N(alkyl)₂), C₅-C₂₄ arylsulfonyl (—SO₂-aryl), boryl (—BH₂), borono(—B(OH)₂), boronato (—B(OR)₂ where R includes without limitation alkylor other hydrocarbyl), phosphono (—P(O)(OH)₂), phospho (—PO₂), phosphino(—PH₂), silyl (—SiR₃ wherein R is H or hydrocarbyl), and silyloxy(—O-silyl); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂alkyl, more preferably C₁-C₆ alkyl), C₂-C₂₄ alkenyl (preferably C₂-C₁₂alkenyl, more preferably C₂-C₆ alkenyl). C₂-C₂₄ alkynyl (preferablyC₂-C₁₂ alkynyl, more preferably C₂-C₆ alkynyl), C₅-C₂₄ aryl (preferablyC₅-C₁₄ aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄aralkyl (preferably C₆-C₁₆ aralkyl).

By “functionalized” as in “functionalized hydrocarbyl”, “functionalizedalkyl”, “functionalized olefin”, “functionalized cyclic olefin”, and thelike, is meant that in the hydrocarbyl, alkyl, olefin, cyclic olefin, orother moiety, at least one H atom bound to a carbon (or other) atom isreplaced with one or more functional groups such as those describedhereinabove. The term “functional group” is meant to include anyfunctional species that is suitable for the uses described herein. Inparticular, as used herein, a functional group would necessarily possessthe ability to react with or bond to corresponding functional groups ona substrate surface.

In addition, the aforementioned functional groups may, if a particulargroup permits, be further substituted with one or more additionalfunctional groups or with one or more hydrocarbyl moieties such as thosespecifically enumerated above. Analogously, the above mentionedhydrocarbyl moieties may be further substituted with one or morefunctional groups or additional hydrocarbyl moieties such as thosespecifically mentioned above. Analogously, the above-mentionedhydrocarbyl moieties may be further substituted with one or morefunctional groups or additional hydrocarbyl moieties as noted above.

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, the phrase “optionally substituted” means that anon-hydrogen substituent may or may not be present on a given atom, and,thus, the description includes structures wherein a non-hydrogensubstituent is present and structures wherein a non-hydrogen substituentis not present.

The term “terminal olefin” as used herein means an olefin wherein one ofthe olefinic carbons (i.e., the carbons of the carbon-carbon doublebond) is substituted by at least one non-hydrogen substituent and theother olefinic carbon is unsubstituted.

The term “nil”, as used herein, means absent or nonexistent.

The term “sulfhydryl” as used herein, represents a group of formula“—SH”.

The term “hydroxyl” as used herein, represents a group of formula “—OH”.

The term “carbonyl” as used herein, represents a group of formula“—C(O)—”.

The term “ketone” as used herein, represents an organic compound havinga carbonyl group linked to a carbon atom such as —C(O)R^(x), whereinR^(x) can be alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle asdefined above.

The term “ester” as used herein, represents an organic compound having acarbonyl group linked to a carbon atom such as —C(O)OR^(x) wherein R^(x)can be alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle as definedabove.

The term “amine” as used herein, represents a group of formula“—NR^(x)R^(y)”, wherein R^(x) and R can be the same or independently H,alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle as defined above.

The term “carboxyl” as used herein, represents a group of formula“—C(O)O—”.

The term “sulfonyl” as used herein, represents a group of formula“—SO₂”.

The term “sulfate” as used herein, represents a group of formula“—O—S(O)₂—O—”.

The term “sulfonate” as used herein, represents a group of the formula“—S(O)₂—O—”.

The term “carboxylic acid” as used herein, represents a group of formula“—C(O)OH”.

The term “nitro” as used herein, represents a group of formula “—NO₂”.

The term “cyano” as used herein, represents a group of formula “—CN”.

The term “amide” as used herein, represents a group of formula“C(O)NR^(x)R^(y)”, wherein R^(x) and R^(y) can be the same orindependently H, alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle asdefined above.

The term “sulfonamide” as used herein, represents a group of formula“—S(O)₂NR^(x)R^(Y)” wherein R^(x) and R^(y) can be the same orindependently H, alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle asdefined above.

The term “sulfoxide” as used herein, represents a group of formula“—S(O)—”.

The term “phosphonic acid” as used herein, represents a group of formula“—P(O)(OH)₂”.

The term “phosphoric acid” as used herein, represents a group of formula“—OP(O)(OH)₂”.

The term “sulphonic acid” as used herein, represents a group of formula“—S(O)₂OH”.

The formula “H”, as used herein, represents a hydrogen atom.

The formula “O”, as used herein, represents an oxygen atom.

The formula “N”, as used herein, represents a nitrogen atom.

The formula “S”, as used herein, represents a sulfur atom.

Functional groups may be protected in cases where the functional groupinterferes with the metathesis catalyst, and any of the protectinggroups commonly used in the art may be employed. Acceptable protectinggroups may be found, for example, in Greene et al., Protective Groups inOrganic Synthesis, 5th Ed. (New York: Wiley, 2014). Examples ofprotecting groups include acetals, cyclic acetals, boronate esters(boronates), cyclic boronate esters (cyclic boronates), carbonates, orthe like. Examples of protecting groups include cyclic acetals or cyclicboronate esters.

SUMMARY

Olefin cross-metathesis is a convergent method for building C—C doublebonds in natural product syntheses. [Cheng-Sánchez, I.; Sarabia, F.Recent Advances in Total Synthesis via Metathesis Reactions. Synthesis2018, 50, 3749-3786. Fürstner, A. Metathesis in Total Synthesis. Chem.Commun. 2011, 47, 6505. Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.Metathesis Reactions in Total Synthesis. Angew. Chrem. Int. Ed. 2005,44, 4490-4527.] However, it has seldom been applied in the previoussyntheses of Δ¹²-PGJ family. Most importantly, conventional metathesiscatalysts typically gave imperfect control of alkene geometry.

Previous syntheses relied on the semi-hydrogenation of alkynes or Wittigreactions, requiring multi-step functional group manipulation withconcomitant waste generation. From a strategic perspective,chemoselectivity among multiple alkenes has also been another concern,especially in the later stages. Stereoselective andalkene-chemoselective metathesis catalysts are in demand to realize aconvergent synthesis from simple alkene building blocks.

A series of cyclometallated ruthenium-based catalysts (e.g. Ru-1, Ru-2)as shown in FIG. 2, were recently developed by Grubbs and co-workers.

The ruthenium catalysts of FIG. 2 enabled Z-selective metathesis througha favored syn-metallocyclobutane intermediate (Scheme 1, Path A).

[Endo, K.; Grubbs, R. H. Chelated Ruthenium Catalysts for Z-SelectiveOlefin Metathesis. J. Am. Chem. Soc. 2011, 133, 8525-8527. Keitz, B. K.;Endo, K.; Patel, P. R.; Herbert, M. B.; Grubbs, R. H. Improved RutheniumCatalysts for Z-Selective Olefin Metathesis. J. Am. Chem. Soc. 2012,134, 693-699.]

More recently, catechodithiolate-based catalyst Ru-3 and its dithiolatevariants were developed by Hoveyda group and showed high Z-selectivityin ring opening metathesis polymerizations, ring-openingcross-metathesis, and cross-metathesis with Z-olefins.

In fact, high kinetic E-selectivity in cross-metathesis with E-startingmaterials was also observed with Ru-3, the s-lPr analogue Ru-4, andother less bulky fast-initiating analogues developed by Materia Inc. andthe Grubbs group, that defined these catalysts as stereoretentive.[Johns, A. M.; Ahmed, T. S.; Jackson, B. W.; Grubbs, R. H.; Pederson, R.L. High Trans Kinetic Selectivity in Ruthenium-Based OlefinCross-Metathesis through Stereoretention. Org. Lett. 2016, 18, 772-775.Ahmed, T. S.; Grubbs, R. H. Fast-Initiating, Ruthenium-Based Catalystsfor Improved Activity in Highly E-Selective Cross Metathesis. J. Am.Chem. Soc. 2017, 139, 1532-1537. Khan, R. K. M.; Torker, S.; Hoveyda, A.H. Readily Accessible and Easily Modifiable Ru-Based Catalysts forEfficient and Z-Selective Ring-Opening Metathesis Polymerization andRing-Opening/Cross-Metathesis. J. Am. Chem. Soc. 2013, 135, 10258-10261.Hoveyda, A. H. Evolution of Catalytic Stereoselective Olefin Metathesis:From Ancillary Transformation to Purveyor of Stereochemical Identity. J.Org. Chem. 2014, 79, 4763-4792. Koh, M. J.; Khan, R. K. M.; Torker, S.;Hoveyda, A. H. Broadly Applicable Z- and DiastemoselectiveRing-Opening/Cross-Metathesis Catalyzed by a Dithiolate Ru Complex.Angew. Chem. Int. Ed. 2014, 53, 1968-1972.]

The origin of the stereoretention was attributed to the formation of aside-bound metallacyclobutane intermediate, of which the α-substituentsare forced down to minimize steric interactions with the bulky N-arylgroups of the NHC. As a result, when starting with Z-alkenes, theβ-substituent points down to generate Z-alkene products (Scheme 1, PathB). When starting with E-alkenes, however, the β-substituent has topoint up into the open space between two N-aryl groups, leading to thegeneration of E-alkene products, albeit with slower rates (Scheme 1,Path C).

Cross-metathesis between two terminal alkenes is not possible withstereoretentive metathesis catalysts however, because the intermediatemethylidene species are unstable and lead to catalyst decomposition.[Koh, M. J.; Khan, R. K. M.; Torker, S.; Yu. M.; Mikus, M. S.; Hoveyda,A. H. High-Value Alcohols and Higher-Oxidation-State Compounds byCatalytic Z-Selective Cross-Metathesis. Nature 2015, 517, 181-186.]

A methylene capping strategy was recently reported as a remedy to thisproblem, enabling the cross-metathesis of two terminal alkenes. [Xu, C.;Shen, X.; Hoveyda, A. H. In Situ Methylene Capping: A General Strategyfor Efficient Stereoretentive Catalytic Olefin Metathesis. The Concept,Methodological Implications, and Applications to Synthesis ofBiologically Active Compounds. J. Am. Chem. Soc. 2017, 139,10919-10928.] Despite the unique properties of these stereoretentivecatalysts, to date, limited synthetic evaluation of these catalysts hasbeen conducted. [Stereoretentive metathesis using Ru: Montgomery, T. P.;Ahmed, T. S.; Grubbs. R. H. Stereoretentive Olefin Metathesis: An Avenueto Kinetic Selectivity. Angew. Chem. Int. Ed 2017, 56, 11024-11036.Ahmed, T. S.; Grubbs, R. H. A Highly Efficient Synthesis ofZ-Macrocycles P.; Grubbs. R. H. Using Stereoretention for the Synthesisof E-Macrocycles with Ruthenium-Based Olefin Metathesis Catalysts. Chem.Sci. 2018, 9, 3580-3583. Jung, K.; Kim, K.; Sung, J.-C.; Ahmed, T. S.;Hong, S. H.; Grubbs, R. H.; Choi, T.-L. Toward Perfect Regiocontrol forβ-Selective Cyclopolymerization Using a Ru-Based Olefin MetathesisCatalyst. Macromolecules 2018, 51, 4564-4571. Stereoretentive metathesisusing Mo, W: Couturier, J.-L.; Paillet, C.; Leconte, M.; Basset, J.-M.;Weiss, K. A Cyclometalated Aryloxy(Chloro) Neopentylidene-tungstenComplex: A Highly Active and Stereoselective Catalyst for the Metathesisof Cis- and Trans-2-Pentene. Norbomene, 1-Methyl-Norbornene, and EthylOleate. Angew. Chem. Int. Ed 1992, 31, 628-631. Lam, J. K.; Zhu, C.;Bukhryakov, V.; Müller, P.; Hoveyda, A.; Schrock, R. R. Synthesis andEvaluation of Molybdenum and Tungsten Monoaryloxide Halide AlkylideneComplexes for Z-Selective Cross-Metathesis of Cyclooctene andZ-1,2-Dichloroethylene. J. Am. Chem. Soc. 2016, 138, 15774-15783.Nguyen, T. T.; Koh, M. J.; Shen, X.; Romiti, F.; Schrock, R. R.;Hoveyda, A. H. Kinetically Controlled E-Selective Catalytic OlefinMetathesis. Science 2016, 352, 569-575. Shen, X.; Nguyen. T. T.; Koh, M.J.; Xu, D.; Speed, A. W. H.; Schrock. R. R.; Hoveyda, A. H. KineticallyE-Selective Macrocyclic Ring-Closing Metathesis. Nature 2017, 541,380-385. Koh. M. J.; Nguyen, T. T.; Lam, J. K.; Torker, S.; Hyvl, J.;Schrock, R. R.; Hoveyda, A. H. Molybdenum Chloride Catalysts forZ-Selective Olefin Metathesis Reactions. Nature 2017, 542, 80-85.]

Herein, we present a total synthesis of the olefin-enrichedΔ¹²-prostaglandin J natural products (1)-(4) of FIG. 1, by implementinga concise stereoretentive metathesis approach. This also sets a perfecttest ground to evaluate the reactivity, chemoselectivity, and functionalgroup compatibility of these newly developed metathesis catalysts.

Retrosynthetically, Δ¹²-PGJ₃ (3) for example, can be simplified into atruncated prostaglandin structure 22 by use of stereoretentivemetathesis (Scheme 2).

A three-component coupling strategy can be applied toward the synthesisof 22, using a relatively simple and commercially available allylGrignard reagent, w-chain aldehyde 21, and a chiral cyclopentenone(R)-6. The O-Boc group of (R)-6 can be used as a tracelessstereoinductive group to set the C8 stereocenter. [Noyori, R.; Suzuki,M. Prostaglandin Syntheses by Three-Component Coupling. Angew. Chem.Int. Ed. 1984, 23, 847-876. Arisetti, N.; Reiser, O. TracelessStereoinduction for the Enantiopure Synthesis ofSubstituted-2-Cyclopentenones. Org. Lett. 2015, 17, 94-97.]

Following the retrosynthetic analysis of Δ¹²-PGJ₃ (3) we aimed tosynthesize Δ¹²-PGJ₂ (1). Therefore, chiral cyclopentenone (R)-6 wasprepared from furfuryl alcohol in a three-step process including akinetic resolution method developed by Reiser and coworkers (Scheme 3).[Ulbrich, K.; Kreitmeier, P.; Vilaivan, T.; Reiser, O. EnantioselectiveSynthesis of 4-Heterosubstituted Cyclopentenones. J. Org. Chem. 2013,78, 4202-4206.]

The ω-chain aldehyde 10 was prepared from hexanal 7 through asymmetricKeck allylation, [Yadav, J. S.; Suresh, B.; Srihari, P. StereoselectiveTotal Synthesis of the Marine Macrolide Sanctolide A: Total Synthesis ofthe Marine Macrolide Sanctolide A. Eur. J. Org Chem. 2015, 201,5856-5863.] The TBS protection, and ozonolysis are also shown in (Scheme4).

With all the starting materials for the three-component coupling inhand, CuBr.Me₂S and LiCl facilitated the diastereoselective conjugateaddition of the allyl magnesium bromide. The enolate formed was trappedby the subsequently added m-chain aldehyde electrophile, and the O-Bocgroup was eliminated in the course of the aldol reaction to form thedesired cyclopentenone.

Elimination with MsCl and DMAP favored E-product 11 as the major productin reasonable yield (45% over 2 steps, Scheme 5).

Stereoretentive metathesis was then evaluated on 11. Since 11 cannotreact with another terminal alkene using stereoretentive metathesiscatalysts, we considered a symmetric Z-alkene 13 as the couplingpartner, which could also be made by homodimerization of readilyavailable 12 through stereoretentive metathesis. With 1 mol % loading ofRu-4 as the catalyst, 98% conversion could be achieved by applyingdynamic vacuum to remove the by-product, cis-3-hexene (bp 66-68° C.)from the reaction mixture. Next, 11 with an additional S mol % catalystRu-4 were added into the reaction mixture, and the alcohol product 14could be isolated in 95% yield in high Z-selectivity (>99% Z). Thisresult established the efficacy of an efficient one-pot, stereoretentivehomodimerization/cross-metathesis strategy to build the CS Z-alkene.

In contrast, synthesis of PGE2 and PGF2a required a large excess ofgaseous butene and more complicated operations in the previouslyreported methylene capping strategy. [Xu, C.; Shen, X.; Hoveyda, A. H.In Situ Methylene Capping: A General Strategy for EfficientStereoretentive Catalytic Olefin Metathesis. The Concept, MethodologicalImplications, and Applications to Synthesis of Biologically ActiveCompounds. J. Am. Chem. Soc. 2017, 139, 10919-10928.] Ley oxidation anddeprotection of the TBS group of 14 in aqueous HF furnished the naturalproduct Δ¹²-prostaglandin J₂ (1) in 89% yield over the last two steps.

The same three-component coupling sequence was performed to obtain 16,and the enal functionality of aldehyde 15 was well tolerated in thealdol step, as shown in Scheme 8.

16 was then subjected to the standard one-pot stereoretentivehomodimerization/cross-metathesis conditions, and alcohol 17 wasobtained in excellent yield (93% yield, Scheme 9) with high2-selectivity (>99% Z). The C14 E-alkene tolerated the reaction,consistent with the much slower reaction of E-alkenes with Ru-4 as seenpreviously. [Johns, A. M.; Ahmed, T. S.; Jackson, B. W.; Grubbs, R. H.;Pederson, R. L. High Trans Kinetic Selectivity in Ruthenium-Based OlefinCross-Metathesis through Stereoretention. Org. Lett. 2016, 18, 772-775.Ahmed, T. S.; Grubbs, R. H. Fast-Initiating. Ruthenium-Based Catalystsfor Improved Activity in Highly E-Selective Cross Metathesis. J. Am.Chem. Soc. 2017, 139, 1532-1537.] We also assessed the enantiopurity ofintermediates 16 and 17. Three-component coupling product 16 proceededwith a small loss in enantiopurity (88% cc) from (R)-6 (>99% ee); butthe metathesis product 17 was obtained without significant erosion ofenantiopurity (87% ee).

This result demonstrates that stereoretentive metathesis with catalystRu-4 also retained the stereochemistry of the C8 stereocenter. Leyoxidation of 17 again gave 15-deoxy-Δ^(12,14)-prostaglandin J₂ (2) in68% yield.

Synthesis of Δ¹²-prostaglandin J₃ (3) began with the preparation of theω-chain aldehyde 21. We envisioned the Z-alkene in 21 could also begenerated from stereoretentive metathesis. First, we obtained chiralalcohol 18 through a reported chiral pool strategy with(R)-epichlorohydrin as the starting material (Scheme 11). [Bai, Y.;Shen, X.; Li, Y.; Dai, M. Total Synthesis of (−)-Spinosyn A viaCarbonylative Macrolactonization. J. Am. Chem. Soc. 2016, 138,10838-1084.]

TBS protection of the alcohol 18 and subsequent removal of the1,3-dithiol gave aldehyde 20. Stereoretentive metathesis of 20 with anexcess amount of cis-3-hexene using catalyst Ru-4 (4 mol %) affordedω-chain aldehyde 21 in good yield (88%) with high Z-selectivity (>99%Z). The short synthesis of aldehyde 21 proved that a broad range offunctional groups, including aldehydes, can be tolerated withoutprotecting group manipulations using stereoretentive catalysts. Then,product 22 was synthesized through the standard three-component couplingsequence from (R)-6 (Scheme 12).

Surprisingly, fast ring closing metathesis (RCM) with Ru-4 yielded 24 asa byproduct (31% yield) bearing an unusual 9-membered ring and thedesired alcohol product 23 was obtained in only 44% yield.

Alternatively, we chose to use cyclometallated catalyst Ru-2 tocircumvent the crossover of alkene reactivity. Because tri-substitutedmetallacyclobutane intermediates are highly unfavorable with thiscyclometallated catalyst, this pathway can be easily avoided FIG. 4.

[Herbert, M. B.; Grubbs, R. H. Z-Selective Cross Metathesis withRuthenium Catalysts: Synthetic Applications and MechanisticImplications. Angew. Chem. Int. Ed 2015, 54, 5018-5024.] Chemoselectivecross-metathesis of 5-hexen-1-ol (25) with the allyl group of 22

furnished the desired product 23 in good yield (52%) with a trace amountof by-product 26 (less than 2%, Scheme 14). The RCM product 24 was notobserved under these conditions.

The side-reaction of C₁₇ internal Z-alkene could be attributed toethylene produced or the residual ruthenium methylidene species in thesolution. Then. Ley oxidation of 23 and deprotection of the TBS groupwith aqueous HF provided Δ¹²-prostaglandin J₃ (3) in 8 linear steps.

Finally, in the synthesis of 15d-PGJ₃ (4)(Scheme 16), crossover ofmetathesis reactivity between the allyl group and the C17 Z-alkene of 28could also be expected. Standard stereoretentive metathesis conditionswith Ru-4 provided desired product 29 in 36% yield and by-products 30and 31.

28 as well as by-products 29 and 30 were obtained using Ru-2 and noimprovement of chemoselectivity was observed. Compared to Δ¹²-PGJ₃ (3)synthesis, where the steric bulk of the OTBS group may be beneficial toachieving good chemoselectivity, 28 has no such steric hindrance.However, no RCM of 28 was observed, possibly due to the ring strain ofthe RCM product. Though 30 could not be separated from 29, the mixturewas subjected to pyridinium chlorochromate (PCC) oxidation and Pinnickoxidation conditions allowing us to isolate15-deoxy-Δ^(12,14)-prostaglandin J₃ (4) (12% yield from 28). Leyoxidation of a mixture of 29 and 30 was also performed but resulted in asignificant amount of decomposition products.

In conclusion, we were able to achieve a concise and convergentsynthesis of four Δ¹²-prostaglandin J natural products in shortersequences (7-8 steps in the longest linear sequences) empowered bystereoretentive and stereoselective metathesis. Furthermore, thereactivity, chemoselectivity, and functional group compatibility ofstereoretentive metathesis was evaluated. This study should inspirefurther practical applications of stereoselective metathesis, such as afacile one-pot stereoretentive homodimerization/cross-metathesisstrategy to introduce Z-alkenes with excellent geometric control. Themodularity and expediency of this chemistry opens the synthesis of otherprostaglandins and analogues to enable SAR studies in cancer treatment.With the well-defined kinetically Z/E-selective catalysts that have beendeveloped to overcome the inherent thermodynamic preference of alkeneproduct geometry, olefin metathesis can play a pivotal role in thesynthesis design.

Olefin Metathesis Catalysts

In one embodiment, the invention provides a stereoretentive rutheniumolefin metathesis catalyst represented by the structure of Formula (I),

wherein:

X is O or S; Y is O or S; Z is N or CR³²;

W is O, halogen, NR³³ or S;R¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R² can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R¹ can form a spire compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —R(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl or together with R² or together with R¹ can form apolycyclic ring or together with R⁴ can form a spiro compound;R⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R³ can form a spiro compound ortogether with R² or together with R¹ can form a polycyclic ring;R⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ can form an optionallysubstituted polycyclic ring;R⁶ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)R², —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁵ or together with R⁷ can form anoptionally substituted polycyclic ring;R⁷ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ or together with R⁸ can form anoptionally substituted polycyclic ring;R⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁷ or together with R⁹ can form anoptionally substituted polycyclic ring;R⁹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁸ can form an optionallysubstituted polycyclic ring;R¹⁰ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹¹ can form an optionallysubstituted polycyclic ring;R¹¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R¹⁰ or together with R¹² can form anoptionally substituted polycyclic ring;R¹² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹¹ or together with R¹³ can form anoptionally substituted polycyclic ring;R¹³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁴ or together with R¹² can form anoptionally substituted polycyclic ring;R¹⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹³ can form a polycyclic ring;R¹⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen. —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁶ can form an optionallysubstituted polycyclic ring;R¹⁶ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁵ or together with R¹⁷ can form anoptionally substituted polycyclic ring;R¹⁷ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁸ or together with R¹⁶ can form anoptionally substituted polycyclic ring;R¹⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁷ can form an optionallysubstituted polycyclic ring;R¹⁹ is H, optionally substituted C₁₋₂₄ alkyl, —C(R³⁴)(R³⁵)COOR³⁶,—C(R³⁴)(R³⁵)C(O)H, —C(R³⁴)(R³⁵)C(O)R³⁷, —C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵)C(O)NR⁴¹R⁴², —C(R³⁴)(R³⁵)C(O)NR⁴¹OR⁴⁰, —C(O)R²⁵, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R³³ can form an optionally substitutedheterocyclic ring or is nil when W is halogen;R²⁰ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ can form a polycyclic ring;R²¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂. —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²⁰ or together with R²¹ can form apolycyclic ring;R²² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²⁰ or together with R²² can form apolycyclic ring:R²² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄, aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ or together with R²³ can form apolycyclic ring;R²³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²² can form a polycyclic ring;R²⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl;R⁷⁵ is OH, OR³⁰, NR²⁷R²⁸, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl,R²⁶ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁷ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁹ is H, optionally substituted C₁₋₂₄ alkyl, OR²⁶, —NR²⁷R²⁸, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl;R³⁰ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³³ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl, optionally substituted C₃₋₈ cycloalkenyl, ortogether with R¹⁹ can form an optionally substituted heterocyclic ring;R³⁴ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted. C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁵ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally, substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁶ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁷ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁹ is H, optionally substituted C alkyl, optionally substituted C₃₋₈cycloalkyl, optionally, substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴⁰ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally, substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl; andx is 1 or 2.

When certain groups, such as: C₁₋₂₄ alkyl, C₃₋₈ cycloalkyl, heterocycle,C₅₋₂₄ aryl, C₃₋₈ cycloalkenyl groups or the polycyclic rings, areoptionally substituted, the substituents are selected from: halogen.—OH, —SH, C₁-C₂₄ alkoxy, C₂-C₂₄ alkenyloxy, C₂-C₂₄ alkynyloxy, C₅-C₂₄aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, —CO—(C₁-C₂₄ alkyl), —CO—(C₆-C₂₄ aryl), —O—CO—(C₁-C₂₄ alkyl), —O—CO—(C₆-C₂₄ aryl),—(CO)—O—(C₁-C₂₄ alkyl), —(CO)—O—(C₆-C₂₄ aryl), (—O—(CO)—O—(C₁-C₂₄alkyl), —O—(CO)—O—(C₆-C₂₄ aryl), (—COOH), (—(CO)—NH₂), (—(CO)—NH(C₁-C₂₄alkyl)), (CO)—N(C₁-C₂₄ alkyl)₂), —(CO)—NH—(C₆-C₂₄ aryl), (—(CO)—N(C₅-C₂₄aryl)₂), (—(CO)—N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), (—(CS)—NH₂),(—(CS)—NH(C₁-C₂₄ alkyl)), (—(CS)—N(C₁-C₂₄ alkyl)₂), —(CS)—NH—(C₅-C₂₄aryl), (—(CS)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄ (—(CS)—N(C₁-C₂₄alkyl)(C₅-C₂₄ aryl), (—NH—(CO)—NH₂), (—C≡N), (—O—C≡N), (—S—C≡N), (—NCO),(—NCS), (—(CO)—H), (—(CS)—H), (—NH₂), (—NH(C₁-C₂₄ ((—N(C₁-C₂₄ alkyl)₂),(—NH(C₅-C₂₄ aryl), (—N(C₅-C₂₄ aryl)₂), —NH—(CO)—(C₁-C₆ alkyl),—NH—(CO)—(C₆-C₂₄ aryl), —C(C₁-C₂₄ alkyl)(NH), (—CHN(C₄-C₂₄ alkyl),(—CHN(C₆-C₂₄ aryl), (—NO₂), (—NO), (—SO₂—OH), —S—(C₁-C₂₄ alkyl),(—S—(C₅-C₂₄ aryl), (—(SO)—(C₁-C₂₄ alkyl), (—(SO)—(C₅-C₂₄ aryl),SO₂—(C₁-C₂₄ alkyl), (—SO₂—N(H)(C₁-C₂₄ alkyl), (—SO₂—N(C₁-C₂₄ alkyl)₂),(—SO₂—(C₅-C₂₄ aryl), (—BH₂), B(OH)₂), (—B(O)(C₁-C₂₄ alkyl)₂,(—P(O)(OH)₂), (PO₂), (—PH₂), —SiH₃, (—O-silyl), C₁-C₂₄ alkyl, C₁-C₁₂alkyl, C₁-C₆ alkyl, C₂-C₂₄ alkenyl, C₂-C₁₂ alkenyl, C₂-C₆ alkenyl,C₂-C₂₄ alkynyl, C₂-C₁₂ alkynyl, C₂-C₆ alkynyl, C₅-C₂₄ aryl, C₅-C₁₄ aryl,C₆-C₂₄ alkaryl, C₆-C₁₆ alkaryl, C₅-C₂₄ aralkyl, and C₅-C₁₆ aralkyl,which are as defined herein.

In another embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N or CR³²; W is O, NR³³ or S;R¹ is H, optionally substituted C₁₋₁₂ alkyl, halogen; R² is H,optionally substituted C₁₋₁₂ alkyl, halogen; R³ is H, optionallysubstituted C₁₋₁₂ alkyl, halogen; is H, optionally substituted C₁₋₁₂alkyl, halogen; R⁵ is H, optionally substituted C₁₋₁₂ alkyl, halogen; R⁶is H, optionally substituted C₁₋₁₂ alkyl, halogen; is H, optionallysubstituted C₁₋₁₂ alkyl, halogen; R⁸ is H, optionally substituted C₁₋₁₂alkyl, halogen; R⁹ is H, optionally substituted C₁₋₁₂ alkyl, halogen;R¹⁰ is H, optionally substituted C₁₋₁₂ alkyl, halogen; is H, optionallysubstituted C₁₋₁₂ alkyl, halogen; R¹² is H, optionally substituted C₁₋₁₂alkyl, halogen; Ria is H, optionally substituted C₁₋₁₂ alkyl, halogen;R¹⁴ is H, optionally substituted C₁₋₁₂ alkyl, halogen; R¹⁵ is H,optionally substituted C₁₋₁₂ alkyl, halogen, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₆-10 aryl or optionally substituted C₃₋₈ cycloalkenyl; R¹⁶is H, optionally substituted C₁₋₁₂ alkyl, halogen, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; R¹⁷ is H, optionally substituted C₁₋₁₂ alkyl, halogen,—optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁸ can form a polycyclic ring; R¹⁸is H, optionally substituted C₁₋₁₂ alkyl, halogen, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl, or together with R¹⁷ can form a polycyclic ring; R¹⁹ is H,optionally substituted C₁₋₁₂ alkyl, —C(R³⁴)(R³⁵)—COOR³⁶,—C(R³⁴)(R³⁵)—C(O)H, —C(R³⁴)(R³⁵)—C(O)R³⁷, —C(R³⁴)(R³⁵)—CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵)—C(O)—NR⁴¹R⁴², —C(R³⁴)(R³⁵)—C(O)—NR⁴¹OR⁴⁰, —C(O)R²⁵,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₆₋₁₀ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R³³ can form an optionallysubstituted heterocyclic ring; R²⁰ is H, optionally substituted C₁₋₁₂alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₆₋₁₀aryl, optionally substituted C₃₋₈ cycloalkenyl or together with R²¹ canform a polycyclic ring; R²¹ is H, optionally substituted C₁₋₁₂ alkyl,halogen, —NR²⁷R²⁸, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₆₋₁₀ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R²⁰ ortogether with R²² can form a polycyclic ring; R²² is H, optionallysubstituted C₁₋₁₂ alkyl, halogen, —C(O)R²¹, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₆₋₁₀ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²¹ or together with R²³ can form apolycyclic ring; R² is H, optionally substituted C₁₋₁₂ alkyl, halogen,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl or together with R² can form a polycyclic ring; R²⁴ isH; R²⁵ is OH, OR³⁰, NR²⁷R²⁸, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁶ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁷ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁸ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁹ is II, optionally substituted C₁₋₁₂ alkyl, OR²⁶,—NR²⁷R²⁸, optionally substituted heterocycle, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted C₆₋₁₀ aryl or optionallysubstituted C₃₋₈ cycloalkenyl; R³⁰ is optionally substituted C₁₋₁₂alkyl, optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³¹ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloakyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³² is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³³ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R can form an optionally substitutedheterocyclic ring; R³⁴ is H, optionally substituted C₆₋₁₀ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁵ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁶ is H, optionally substituted C₁₋₁₂ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₆₋₁₀ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁷ is optionally substituted C₁₋₁₂ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁸ is H, optionally substituted C₁₋₁₂ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁹ is H, optionally substituted C₁₋₁₂ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴⁰ is H, optionally substituted C₁₋₁₂ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴¹ is H, optionally substituted C₁₋₁₂ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴² is H, optionally substituted C₁₋₁₂ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₆₋₁₀ aryl or optionally substituted C₃₋₈cycloalkenyl; and x is 1 or 2.

In another embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N or CR³²; W is O or NR³²; R¹is H, linear or branched C₁₋₆ alkyl, or halogen; R² is H linear orbranched C₁₋₆ alkyl, or halogen; R³ is H, linear or branched C₁₋₆ alkyl,or halogen; R⁴ is H, linear or branched C₁₋₆ alkyl or halogen; R⁵ is H,linear or branched C₁₋₆ alkyl; R⁶ is H, linear or branched C₁₋₆ alkyl;R⁷ is H, linear or branched C₁₋₆ alkyl; R⁸ is H or C₁₋₆ alkyl; R⁹ is H,linear or branched C₁₋₆ alkyl; R¹⁰ is H, linear or branched C₁₋₆ alkyl;R¹¹ is H, linear or branched C₁₋₆ alkyl; R¹² is H, linear or branchedC₁₋₆ alkyl; R¹³ is H, linear or branched C₁₋₆ alkyl or together with R¹⁴forms a naphthyl ring; R¹⁴ is H, linear or branched C₁₋₆ alkyl ortogether with R¹³ forms a naphthyl ring; R¹⁵ is H, phenyl, linear orbranched C₁₋₆ alkyl, halogen or together with R¹⁶ forms a naphthyl ring;R¹⁶ is H, phenyl, linear or branched C₁₋₆ alkyl, halogen or togetherwith R¹⁵ or together with R¹⁷ forms a naphthyl ring; R¹⁷ is H, phenyl,linear or branched C₁₋₆ alkyl, halogen or together with R¹⁶ or togetherwith R¹⁸ forms a naphthyl ring; R¹⁸ is H, phenyl, linear or branchedC₁₋₆ alkyl, halogen or together with R¹⁶ or together with R¹⁸ forms anaphthyl ring; R¹⁹ is H, phenyl, C₁₋₆ alkyl, —C(R³⁴)(R³⁵) COOR³⁶,—C(R³⁴)(R³⁵) C(O)H, —C(R³⁴)(R³⁵) C(O)R³⁷, —C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵) C(O) NR⁴¹R⁴², —C(R³⁴)(R³⁵) C(O) NR⁴¹OR⁴⁰ or together withR³³ forms a five, six or seven membered heterocyclic ring; R²⁰ is H,linear or branched C₁₋₆ alkyl, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃,—S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, pyridine, piperidine,imidazole, indolizine, indazole, optionally substituted C₃₋₈ cycloalkyl,phenyl, naphthalene, cyclohexene or together with R²¹ can form apolycycle; R²¹ is H, phenyl, —NR²⁷R²⁸, linear or branched C₁₋₆ alkyl,halogen or together with R²⁰ or together with R²² can form a polycycle;R²² is H, linear or branched C₁₋₆ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁸R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,pyridine, piperidine, imidazole, indolizine, indazole, optionallysubstituted C₃₋₈ cycloalkyl, phenyl, naphthalene, cyclohexene ortogether with R²¹ or together with R²³ can form a polycycle; R²³ is H,phenyl, linear or branched C₁₋₆ alkyl or together with R²² can form apolycycle; R²⁴ is H, linear or branched C₁₋₆ alkyl; R²⁵ is OH, OR³⁰,NR²⁷R²⁸, linear or branched C₁₋₆ alkyl; R²⁶ is H, linear or branchedC₁₋₆ alkyl; R²⁷ is H, linear or branched C₁₋₆ alkyl; R²⁸ is H, linear orbranched C₁₋₆ alkyl; R²⁹ is H, linear or branched C₁₋₆ alkyl, —NR²⁷R²⁸;R³⁰ is optionally substituted C₁₋₆ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedphenyl or optionally substituted C₃₋₈ cycloalkenyl; R³¹ is H, linear orbranched C₁₋₆ alkyl; R³² is H, linear or branched C₁₋₆ alkyl; R³³ is H,linear or branched C₁₋₆ alkyl, or together with R¹⁹ forms a five, six orseven membered heterocyclic ring; R³⁴ is H, or linear or branched C₁₋₆alkyl; R³³ is H, or linear or branched C₁₋₆ alkyl; R³⁶ is H, linear orbranched C₁₋₆ alkyl; R³⁷ is linear or branched C₁₋₆ alkyl; R³⁸ is H orlinear or branched C₁₋₆ alkyl; R³⁹ is H, linear or branched C₁₋₆ alkyl;R⁴⁰ is H, linear or branched C₁₋₆ alkyl; R⁴¹ is H, linear or branchedC₁₋₆ alkyl; R⁴² is H, linear or branched C₁₋₆ alkyl; and x is 1 or 2.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N or CR³²; W is O, NR³³ or S;R¹ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R² is Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, s-Bu or H; R³ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, ors-Bu; R⁴ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁵ is H, F, Cl,Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁶ is H, F, Cl, Br, I,Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁷ is H, F, Cl, Br, I, Me, Et,i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁸ is H, F, Cl, Br, I, Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, or s-Bu; R⁹ is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, or s-Bu; R¹⁰ is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu,t-Bu, or s-Bu; R¹¹ is H, Me, F, Cl, Br, I, Et, i-Pr, n-Pr, n-Bu, t-Bu,or s-Bu; R¹² is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, ors-Bu; R¹³ is H, Me, F, Cl, Br, I, Et, n-Pr, i-Pr, n-Bu, t-Bu or s-Bu;R¹⁴ is F, Cl, Br, I, Me, lit, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R¹⁵ isH, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, F, Br, I, Cl, or together withR¹⁶ forms a naphthyl or a phenanthryl ring; R¹⁶ is H, F, Cl, Br, I, ortogether with R¹⁵ forms a naphthyl or a phenanthryl ring; R¹⁷ is H, F,Cl, Br, I, or together with R¹⁸ forms a naphthyl, or a phenanthryl ring;R¹⁸ is H, Cl, F, Br, I, 3,5-dichloro-phenyl, phenyl, Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, s-Bu or together with R¹⁷ forms a naphthyl, or aphenanthryl; R is H, phenyl, C₁₋₆ alkyl, —C(R³⁴)(R³⁵) COOR³⁶,—C(R³⁴)(R³⁵) C(O)H, —C(R³⁴)(R³⁵) C(O)R³⁷, —C(R³⁴)(R³⁵) CR³⁸(OR³⁹)(OR⁴⁰),C(R³⁴)(R³⁵), —C(R³⁴)(R³⁵) C(O) NR⁴¹R⁴², —C(R³⁴)(R³⁵) C(O) NR⁴¹OR⁴⁰; R²⁰is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, —C(O)R²⁵,—OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH),—SR³¹, pyridine, piperidine, imidazole, indolizine, indazole, optionallysubstituted C₃₋₈ cycloalkyl, phenyl, naphthalene, or cyclohexene; R²¹ isH, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, —NR²⁷R²⁸F, Cl, Br, orI; R²² is H, Me, Et, i-Pr, halogen. —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, pyridine, piperidine,imidazole, indolizine, indazole, cyclohexyl, phenyl, naphthalene,cyclohexene F, Cl, Br, or I; R²² is H, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸,NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, or —SR³¹; R²³ is H, F,Cl, Br, I, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁴ is H; R²is H, or Me; R²⁵ is OH, OR³⁰, NR²⁷R²⁸, Me, Et, or i-Pr; R²⁶ is H, Me,Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁷ is H. Me, Et, or i-Pr; R²⁸ isH. Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁹ is H, Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, s-Bu, or —NR²⁷R²⁸; R³⁰ is Me, Et, i-Pr, n-Pr, n-Bu,t-Bu, or s-Bu; R³¹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³² isMe, Et, n-Pr or H; R³³ is H, Me, Et, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu,s-Bu, or together with R¹⁹ forms a morpholino, a thio-morpholino, apyrrolidino, a piperidino, or a piperazino ring; R³⁴ is H, Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, or s-Bu; R³⁵ is H, or Me, E, i-Pr, n-Pr, n-Bu, t-Bu,or s-Bu; R³⁶ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³⁷ is Me,Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³⁸ is H or Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, or s-Bu; R³⁹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu;R⁴⁰ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁴¹ is H, Me, Et,i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁴² is H, Me, Et, i-Pr, n-Pr, n-Bu,t-Bu, or s-Bu; and x is 1 or 2.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is Me or H; R²is Me or H; R³ is H; R⁴ is H; R⁵ is H, F, Me, t-Bu or i-Pr; R⁶ is H ort-Bu; R⁷ is H, F or Me; R⁸ is H, F or t-Bu; R⁹ is H, F, Me, t-Bu ori-Pr; R¹⁰ is H, F, Me, t-Bu or i-Pr; R¹¹ is H or t-Bu; R¹² is H, F orMe; R¹³ is H, F or t-Bu; R¹⁴ is F, Me, i-Pr, t-Bu or H; R¹⁵ is H, Me, F.Br, I, Cl, or together with R¹⁶ forms a naphthyl; R¹⁶ is H, or togetherwith R¹⁵ forms a naphthyl; R¹⁷ is H or together with R¹⁸ forms anaphthyl, or a phenanthryl ring; R¹⁸ is Cl, F, Br, I,3,5-dichloro-phenyl, phenyl, t-Bu or together with R¹⁷ forms a naphthyl,or a phenanthryl ring; R¹⁹ is i-Pr; R²⁰ is H or phenyl; R²¹ is H; R²² isH, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹; R²³ is H; R²⁴ is H; R²⁵ is OH, OR³⁰, NR²⁷R²⁸, Me,Pt, or i-Pr; R²⁶ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁷ isH, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁸ is H, Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, or s-Bu; R²⁹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu,s-Ba, —NR²⁷R²⁸; R³⁰ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; and R³¹is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is Me; R² is Me;R³ is H; R⁴ is H; R⁵ is F; R⁶ is H; R⁷ is H or F; R⁸ is H; R⁹ is F; R¹⁰is F; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is F; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; Ra is phenyl; R²⁰ is H; R²¹ is H; R²² isH; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ isMe; R¹¹ is H; R¹² is Me; R¹³ is H; R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is phenyl; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is phenyl; R²¹ is H; R²² is H; R²³is H; and R²⁴ is H.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is Me; R² is Me;R³ is H; R⁴ is H; R⁵ is F; R⁶ is H; R⁷ is H or F; R⁸ is H; R⁹ is F; R¹⁰is F; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is F; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ is H;and R²⁴ is H.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is HI; R² is H;R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ isMe; R¹¹ is H; R¹² is Me; R¹³ is H; R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ is H;and R²⁴ is H.

In one embodiment, the invention provides a catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.

In one embodiment the invention provides a compound wherein the moiety

of Formula (I) is

and wherein, R⁴³ is optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₄ cycloalkyl, optionally substituted C₅₋₂₄ aryl oroptionally substituted C₃₋₈ cycloalkenyl, and “f” is 0, 1, 2, 3, or 4.

In one embodiment, the invention provides a compound wherein the moiety

of Formula (I) is

and wherein R¹⁹, R²⁰, R²⁷, R²⁸, R⁴³ and “f” are as defined herein.

In one embodiment, the invention provides a compound wherein the moiety

In one embodiment, the invention provides a compound of Formula (I) isselected from:

In one embodiment, the invention provides a Z-selective ruthenium olefinmetathesis catalyst represented by the structure of Formula (V),

wherein,W is O, halogen, NR³³ or S;X¹ is hydrogen, halide, nitrate, optionally substituted C₁-C₂₀ alkyl,optionally substituted C₅-C₂₄ aryl, optionally substituted C₁-C₂₀alkoxy, optionally substituted C₁-C₂₀ alkylcarboxylate, optionallysubstituted C₅-C₂₄ aryloxy, optionally substituted C₂-C₂₀alkoxycarbonyl, optionally substituted C₆-C₂₄ aryloxycarbonyl,optionally substituted C₆-C₂₄ arylcarboxylate, optionally substitutedC₂-C₂₄ acyl, optionally substituted C₂-C₂₄ acyloxy, optionallysubstituted C₁-C₂₀ alkylsulfonato, optionally substituted C₅-C₂₄arylsulfonato, optionally substituted C₁-C₂₀ alkylsulfanyl, optionallysubstituted C₅-C₂₄ arylsulfanyl, optionally substituted C₁-C₂₀alkylsulfinyl, or optionally substituted C₅-C₂₄ arylsulfinyl;R¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R² can form a spiro compound ortogether with R; or together with R⁴ can form a polycyclic ring;R² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R¹ can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl or together with R² or together with R¹ can form apolycyclic ring or together with R⁴ can form a spiro compound;R⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₁₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R³ can form a spiro compound ortogether with R² or together with R¹ can form a polycyclic ring;R⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃. —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ can form an optionallysubstituted polycyclic ring;R⁶ is H, optionally substituted C₁₋₂₄ alkyl, halogen. —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁵ or together with R⁷ can form anoptionally substituted polycyclic ring;R⁷ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ or together with R⁸ can form anoptionally substituted polycyclic ring;R⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁷ or together with R⁹ can form anoptionally substituted polycyclic ring;R⁹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃. —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁸ can form an optionallysubstituted polycyclic ring;R¹⁹ is H, optionally substituted C₁₋₂₄ alkyl, —C(R³⁴)(R³⁵)COOR³⁶,—C(R³⁴)(R³⁵)C(O)H, —C(R³⁴)(R³⁵)C(O)R³⁷, —C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵)C(O)NR⁴¹R⁴², —C(R³⁴)(R³⁵)C(O)NR⁴¹OR⁴², —C(O)R²⁵, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R³³ can form an optionally substitutedheterocyclic ring or is nil when W is halogen;R²⁰ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ can form a polycyclic ring;R²¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²⁰ or together with R²² can form apolycyclic ring;R²² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ or together with R²³ can form apolycyclic ring;R²³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²² can form a polycyclic ring;R²⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl;R²⁵ is OH, OR³⁰, NR²⁷R²⁸, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl,R²⁶ is ii, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₁₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁷ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁹ is H, optionally substituted C₁₋₂₄ alkyl, OR²⁶, —NR²⁷R²⁸, optionallysubstituted heterocycle, optionally substituted C₃₋₄ cycloalkyl,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl;R³⁰ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³³ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl, optionally substituted C₃₋₈, cycloalkenyl, ortogether with R can form an optionally substituted heterocyclic ring;R³⁴ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³⁵ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³⁶ is H, optionally substituted C₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³⁷ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³⁸ is H, optionally substituted C₁₋₁₂ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁹ is H, optionally substituted C₁₋₁₂ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴⁰ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R⁴² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;x is 1 or 2; and wherein the adamantyl can be optionally substituted byone or more C₁₋₆ alkyl groups.

In one embodiment, the invention provides a stereoretentive rutheniumolefin metathesis catalyst represented by the structure of Formula (V),wherein: W is O; X¹ is benzoate, pivalate, C₁-C₆ acyl, C₂-C₆alkoxycarbonyl, C₁-C₆ alkyl, phenoxy, C₁-C₆ alkoxy, C₁-C₆ alkylsulfanyl,aryl, or C₁-C₆ alkylsulfonyl; R¹ is H, optionally substituted C₁₋₁₂alkyl, halogen; R² is H, optionally substituted C₁₋₁₂ alkyl, halogen; R³is H, optionally substituted C₁₋₁₂ alkyl, halogen; R⁴ is H, optionallysubstituted C₁₋₁₂ alkyl, halogen; R⁵ is H, optionally substituted C₁₋₁₂alkyl, halogen; R⁶ is H, optionally substituted C₁₋₁₂ alkyl, halogen; R⁷is H, optionally substituted C₁₋₁₂ alkyl, halogen; R⁸ is H, optionallysubstituted C₁₋₁₂ alkyl, halogen; R⁹ is H, optionally substituted C₁₋₁₂alkyl, halogen; R¹⁹ is H, optionally substituted C₁₋₁₂ alkyl,—C(R³⁴)(R³⁵)—COOR³⁶, —C(R³⁴)(R³⁵)—C(O)H, —C(R³⁴)(R³⁵)—C(O)R³⁷,—C(R³⁴)(R³⁵)—CR³⁸(OR³⁹)(OR⁴⁰), —C(R³⁴)(R³⁵)—C(O)—NR⁴¹R⁴²,—C(R³⁴)(R³⁵)—C(O)—NR⁴¹OR⁴⁰, —C(O)R²⁵, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₆₋₁₀ aryl, optionally substituted C₃₋₈ cycloalkenyl ortogether with R³³ can form an optionally substituted heterocyclic ring;R²⁰ is H, optionally substituted C₁₋₁₂ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₆₋₁₀ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ can form a polycyclic ring; R²¹is H, optionally substituted C₁₋₁₂ alkyl, halogen, —NR²⁷R²⁸, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₆₋₁₀ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²⁰ or together with R²² can form apolycyclic ring; R²² is H, optionally substituted C₁₋₁₂ alkyl, halogen,—C(O)R²⁵—, OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₆₋₁₀ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R²¹ ortogether with R²³ can form a polycyclic ring; R²³ is H, optionallysubstituted C₁₋₁₂ alkyl, halogen, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₆₋₁₀aryl or optionally substituted C₃₋₈ cycloalkenyl or together with R²²can form a polycyclic ring; R²⁴ is H; R²⁵ is OH, OR³⁰, NR²⁷R²⁸,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁶ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁷ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁸ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁹ is H,optionally substituted C₁₋₁₂ alkyl, OR, —NR²⁷R²⁸, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³⁰is optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³¹ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³² is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³³ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl, or together withR¹⁹ can form an optionally substituted heterocyclic ring; R³⁴ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₄ cycloalkenyl; R³⁵ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³⁶ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³⁷ isoptionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³⁸ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R³⁹ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R⁴⁰ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R⁴¹ is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; R⁴² is H,optionally substituted C₁₋₁₂ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₆₋₁₀ aryl or optionally substituted C₃₋₈ cycloalkenyl; x is 1 or 2; andwherein the adamantyl can be optionally substituted by one or more C₁₋₆alkyl groups.

In another embodiment, the invention provides a catalyst represented byFormula (V) wherein: W is O; X¹ is CF₃CO₂, CH₃CO₂, CH₃CH₂CO₂, CFH₂CO₂,(CH₃)₃CO₂, (CH₃)₂CHCO₂, (CF₃)₂(CH₃)CO₂, (CF₃)(CH₃)₂CO₂, benzoate,naphthylate, tosylate, mesylate, or trifluoromethane-sulfonate; R¹ is H,linear or branched C₁₋₆ alkyl, or halogen; R² is H linear or branchedC₁₋₆ alkyl, or halogen; R³ is H, linear or branched C₁₋₆ alkyl, orhalogen; R⁴ is H, linear or branched C₁₋₆ alkyl or halogen; R⁵ is H,linear or branched C₁₋₆ alkyl; R⁶ is linear or branched C₁₋₆ alkyl; R⁷is H, linear or branched C₁₋₆ alkyl; R⁸ is H or C₁₋₆ alkyl; R⁹ is H,linear or branched C₁₋₆ alkyl; R¹⁹ is H, phenyl, C₁₋₆ alkyl,—C(R³⁴)(R³⁵) COOR³⁶, —C(R³⁴)(R³⁵) C(O)H, —C(R³⁴)(R³⁵) C(O)R³⁷,—C(R³⁴)(R³⁵) CR³⁸(OR³⁹)(OR⁴⁰), —C(R³⁴)(R³⁵) C(O) NR⁴¹R⁴², —C(R³⁴)(R³⁵)C(O) NR⁴¹OR⁴⁰ or together with R³³ forms a five, six or seven memberedheterocyclic ring; R²⁰ is H, linear or branched. C₁₋₆ alkyl, —C(O)R²⁵,—OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂,—SR³¹, pyridine, piperidine, imidazole, indolizine, indazole, optionallysubstituted C₃₋₈ cycloalkyl, phenyl, naphthalene, cyclohexene ortogether with R²¹ can form a polycycle; R²¹ is H, phenyl, —NR²⁷R²⁸,linear or branched C₁₋₆ alkyl, halogen or together with R²⁰ or togetherwith R²² can form a polycycle; R²² is H, linear or branched C₁₋₆ alkyl,halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, pyridine, piperidine, imidazole,indolizine, indazole, optionally substituted C₃₋₈ cycloalkyl, phenyl,naphthalene, cyclohexene or together with R²¹ or together with R²³ canform a polycycle; R²³ is H, phenyl, linear or branched C₁₋₆ alkyl ortogether with R²² can form a polycycle; R²⁴ is H, linear or branchedC₁₋₆ alkyl; R²⁵ is OH, OR³⁰, NR²⁷R²⁸, linear or branched. C₁₋₆ alkyl;R²⁶ is H, linear or branched C₁₋₆ alkyl; R²⁷ is H, linear or branchedC₁₋₆ alkyl; R²⁵ is H, linear or branched C₁₋₆ alkyl; R²⁹ is H, linear orbranched C₃₋₆ alkyl, —NR²⁷R²⁸; R³⁰ is optionally substituted C₁₋₆ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted phenyl or optionally substitutedC₃₋₈ cycloalkenyl; R³¹ is H, linear or branched C₁₋₆ alkyl; R³² is H,linear or branched C₁₋₆ alkyl; R³³ is H, linear or branched C₁₋₆ alkyl,or together with R¹⁹ forms a five, six or seven membered heterocyclicring; R³⁴ is H, or linear or branched C₁₋₆ alkyl; R³⁵ is H, or linear orbranched C₁₋₆ alkyl; R³⁵ is H, linear or branched C₁₋₆ alkyl; R³¹ islinear or branched C₁₋₆ alkyl; R³⁸ is H or linear or branched C₁₋₆alkyl; R³⁹ is H, linear or branched C₁₋₆ alkyl; R⁴⁰ is H, linear orbranched C₁₋₆ alkyl; R⁴¹ is H, linear or branched C₁₋₆ alkyl; R⁴² is H,linear or branched C₁₋₆ alkyl; x is 1 or 2; and wherein the adamantylcan be optionally substituted by one or more C₁₋₆ alkyl groups.

In one embodiment, the invention provides a catalyst represented byFormula (V) wherein: W is O; X¹ is CF₃CO₂, CH₃CO₂, CH₃CH₂CO₂, CFH₂CO₂,(CH₃)₃CO₂, (CH₃)₂CHCO₂, (CF₃)₂(CH₃)CO₂, (CF₃)(CH₃)₂CO₂, benzoate,naphthylate, tosylate, mesylate, or trifluoromethane-sulfonate; R¹ isMe, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R² is Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, s-Bu or H; R³ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu;R⁴ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁴ is H, F, Cl, Br, I,Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁶ is H, F, Cl, Br, I, Me, Et,i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁷ is H, F, Cl, Br, I, Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, or s-Bu; R⁸ is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, or s-Bu; R⁹ is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu,t-Bu, or s-Bu; R¹⁹ is H, phenyl, C₁₋₆ alkyl, —C(R³⁴)(R³⁵) COOR³⁶,—C(R³⁴)(R³⁵) C(O)H, —C(R³⁴)(R³⁵) C(O)R³⁷, —C(R³⁴)(R³⁵) CR³⁸(OR³⁹)(R⁴⁰),—C(R³⁴)(R³⁵) C(O) NR⁴¹R⁴², —C(R³⁴)(R³⁵) C(O) NR⁴¹OR⁴⁰; R²⁰ is H, F, Cl,Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,pyridine, piperidine, imidazole, indolizine, indazole, optionallysubstituted C₃₋₈ cycloalkyl, phenyl, naphthalene, or cyclohexene; R²¹ isH, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, —NR²⁷R²⁸F, Cl, Br, orI; R²² is H, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂. —OP(O)(OH)₂, or —SR³¹; R²³ is H, F, Cl, Br, I, phenyl, Me,Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁴ is H; R²⁴ is H, or Me; R²⁵ isOH, OR, NR²⁷R²⁸, Me, Et, or i-Pr; R²⁶ is H, Me, Et, i-Pr, n-Pr, n-Bu,t-Bu, or s-Bu; R²⁷ is H. Me, Et. or i-Pr; R²⁸ is H, Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, or s-Bu; R²⁹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, or—NR²⁷R²⁸; R³⁰ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³¹ is H, Me,Et, i-Pr, n-Pr, n-Bu, t-Bu. or s-Bu; R³² is Me, Et, n-Pr or H; R³³ is H,Me, Et, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, or together with R¹⁹ formsa morpholino, a thio-morpholino, a pyrrolidino, a piperidino, or apiperazino ring; R³⁴ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³⁵is H, or Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³⁶ is H, Me, Et,i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³⁷ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu,or s-Bu; R³⁸ is H or Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R³⁹ is H,Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R⁴⁰ is H, Me, Et, i-Pr, n-Pr,n-Bu, t-Bu, or s-Bu; R⁴¹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu;R⁴² is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; x is 1 or 2; andwherein the adamantyl can be optionally substituted by one or more Megroups.

In one embodiment, the invention provides a catalyst represented byFormula (V) wherein: W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is H, F, Me, Et, or i-Pr; R⁶ is H, F, Me, Et, or i-Pr; R⁷ isH. F, Me, Et, or i-Pr; R⁸ is H, F, Me, Et, or i-Pr; R⁹ is H, F, Me, Et,or i-Pr; R¹⁹ is H, phenyl, C₁₋₆ alkyl, —C(R³⁴)(R³⁵) COOR³⁶, —C(R³⁴)(R³⁵)C(O)H, —C(R³⁴)(R³⁵) C(O)R³⁷, —C(R³⁴)(R³⁵) CR³⁸(OR³⁹)(OR⁴⁰), —C(R³⁴)(R³⁵)C(O) NR⁴¹R⁴², —C(R³⁴)(R³⁵) C(O) NR⁴¹OR⁴⁰; R²⁰ is H, F, Me, Et, or i-Pr,R²¹ is H, F, Me, Et, or i-Pr, R²² is H, —C(O)R²⁵, —OR²⁶, CN. —NR²⁷R²⁸,NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)OH)₂, —OP(O)(OH)₂, or —SR³¹; R²³ is H, F,Me, Et, or i-Pr; R²⁴ is H; R²⁵ is OH, OR³⁰, NR²⁷R²⁸, Me, Et, or i-Pr;R²⁶ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁷ is H, Me, Et, ori-Pr; R²⁸ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R²⁹ is H, Me,Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, or —NR²⁷R²⁸; R³⁰ is Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, or s-Bu; R³¹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu. ors-Bu; R³² is Me, Et, n-Pr or H; R³⁴ is H, F, Me, Et, or i-Pr; R³⁵ is H,F, Me, Et, or i-Pr, R³⁶ is H, F, Me, Et, or i-Pr; R³⁷ is Me, Et, i-Pr,n-Pr, n-Bu, t-Bu, or s-Bu; R³⁸ is H. F, Me, Et, or i-Pr; R³⁹ is H, F,Me, Et, or I—Pr; R⁴⁰ is H, F, Me, Et, or i-Pr; R⁴¹ is H, F, Me, Et, ori-Pr, and R⁴² is H, F, Me, Et, or i-Pr.

In one embodiment, the invention provides a catalyst represented byFormula (V) wherein: W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a catalyst represented byFormula (V) wherein: W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is i-Pr, R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a compound of Formula (V) isselected from:

It will be appreciated that the amount of catalyst that is used (i.e.,the “catalyst loading”) in the reaction is dependent upon a variety offactors such as the identity of the reactants and the reactionconditions that are employed. It is therefore understood that catalystloading may be optimally and independently chosen for each reaction. Ingeneral, however, the catalyst will be present in an amount that rangesfrom a low of about 0.1 ppm, 1 ppm, or 5 ppm, to a high of about 10 ppm,15 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 500 ppm, or 1000 ppm relativeto the amount of an olefinic substrate.

The catalyst will generally be present in an amount that ranges from alow of about 0.00001 mol %, 0.0001 mol %, or 0.0005 mol %, to a high ofabout 0.001 mol %, 0.0015 mol %, 0.0025 mol %, 0.005 mol %, 0.01 mol %,0.02 mol %, 0.05 mol %, or 0.1 mol % relative to the olefinic substrate.

When expressed as the molar ratio of olefin to catalyst, the catalyst(the “olefin to catalyst ratio”), loading will generally be present inan amount that ranges from a low of about 10,000,000:1, 1,000,000:1,500,000:1 or 200,00:1, to a high of about 100,000:1 60,000:1, 50,000:1,45,000:1, 40,000:1, 30,000:1, 20,000:1, 10,000:1, 5,000:1, or 1,000:1.

EMBODIMENTS

These and other aspects of the invention will be apparent to the skilledartisan in light of the following detailed description and examples.

The invention provides a method that produces a compound (i.e., aproduct, olefin product; e.g., cross-metathesis product) having at leastone carbon-carbon double bond (e.g., a product internal olefin) in a Z/Eselectivity ratio of 95/5, or 96/4, or 97/3, or 98/2, or 99/1. In somecases, 100% of the at least one carbon-carbon double bond produced inthe cross-metathesis reaction has a Z-configuration.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprisingsubmitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I) or in the presence of aZ-selective ruthenium olefin metathesis catalyst represented by Formula(V); wherein R^(v) is selected from

and wherein the stereoretentive ruthenium olefin metathesis catalystrepresented by Formula (I) is

X is O or S; Y is O or S; Z is N or CR³²;

W is O, halogen, NR³³ or S;R¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R^(2S),—OR¹⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂.—SR³¹, optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R² can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R³⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R¹ can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl or together with R² or together with R¹ can form apolycyclic ring or together with R⁴ can form a spiro compound;R⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R³ can form a spiro compound ortogether with R² or together with R¹ can form a polycyclic ring;R⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ can form an optionallysubstituted polycyclic ring;R⁶ is H, optionally substituted C₁₋₁₂ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂. —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁵ or together with R⁷ can form anoptionally substituted polycyclic ring;R⁷ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁷ or together with R⁹ can form anoptionally substituted polycyclic ring;R⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁷ or together with R⁹ can form anoptionally substituted polycyclic ring;R⁹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁸ can form an optionallysubstituted polycyclic ring;R¹⁰ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)R, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹¹ can form an optionallysubstituted polycyclic ring;R¹¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R¹⁰ or together with R¹² can form anoptionally substituted polycyclic ring;R¹² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹¹ or together with R¹³ can form anoptionally substituted polycyclic ring;R¹³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁴ or together with R¹² can form anoptionally substituted polycyclic ring;R¹⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹³ can form a polycyclic ring;R¹⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁶ can form an optionallysubstituted polycyclic ring;R¹⁶ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁵ or together with R¹⁷ can form anoptionally substituted polycyclic ring;R¹⁷ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈, cycloalkenyl, or together with R¹⁸ or together with R¹⁶ can forman optionally substituted polycyclic ring;R¹⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁷ can form an optionallysubstituted polycyclic ring;R¹⁹ is H, optionally substituted C₁₋₂₄ alkyl, —C(R³⁴)(R³⁵)COOR³⁶,—C(R³⁴)(R³⁵)C(O)H, —C(R³⁴)(R³⁵)C(O)R³⁷, —C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵)C(O)NR⁴¹R⁴², —C(R³⁴)(R³⁵)C(O)NR⁴¹OR⁴⁰, —C(O)R²⁵, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R³³ can form an optionally substitutedheterocyclic ring or is nil when W is halogen;R²⁰ is H, optionally, substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ can form a polycyclic ring;R²¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²⁰ or together with R²² can form apolycyclic ring;R²² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²¹ or together with R²³ can form apolycyclic ring;R²³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²² can form a polycyclic ring;R²⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl;R²⁵ is OH, OR³⁰, NR²⁷R²⁸, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl,R²⁶ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁷ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁸ is H, optionally substituted C₁₋₁₂ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁹ is H, optionally substituted C₁₋₂₄ alkyl, OR²⁶, —NR²⁷R²⁸, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl;R³⁰ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³³ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl, optionally substituted C₃₋₈ cycloalkenyl, ortogether with R¹⁹ can form an optionally substituted heterocyclic ring;R³⁴ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁵ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁶ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl:R³⁷ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁸ is H, optionally substituted C₁₋₁₂ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted CM cycloalkenyl;R³⁹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴⁰ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;x is 1 or 2; and wherein the Z-selective ruthenium olefin metathesiscatalyst represented by Formula (V) is

wherein:W is O, halogen, NR³³ or S;X¹ is hydrogen, halide, nitrate, optionally substituted C₁-C₂₀ alkyl,optionally substituted C₅-C₂₄ aryl, optionally substituted C₁-C₂₀alkoxy, optionally substituted C₁-C₂₀ alkylcarboxylate, optionallysubstituted C₅-C₂₄ aryloxy, optionally substituted C₂-C₂₀alkoxycarbonyl, optionally substituted C₆-C₂₄ aryloxycarbonyl,optionally substituted C₆-C₂₄ arylcarboxylate, optionally substitutedC₂-C₂₄ acyl, optionally substituted C₂-C₂₄ acyloxy, optionallysubstituted C₁-C₂₀ alkylsulfonato, optionally substituted C₅-C₂₄arylsulfonato, optionally substituted C₁-C₂₀ alkylsulfanyl, optionallysubstituted C₅-C₂₄ arylsulfanyl, optionally substituted C₁-C₂₀alkylsulfinyl, or optionally substituted C₅-C₂₄ arylsulfinyl;R¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R² can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R² can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring;R³ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl or together with R² or together with R¹ can form apolycyclic ring or together with R⁴ can form a spiro compound;R⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²—, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₁₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R³ can form a spiro compound ortogether with R² or together with R¹ can form a polycyclic ring;R⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶.CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ can form an optionallysubstituted polycyclic ring;R⁶ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₄cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁵ or together with R⁷ can form anoptionally substituted polycyclic ring;R⁷ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂—SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ or together with R⁸ can form anoptionally substituted polycyclic ring:R⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶CN,NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁷ or together with R⁹ can form anoptionally substituted polycyclic ring;R⁹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted. C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁸ can form an optionallysubstituted polycyclic ring;R¹⁹ is H, optionally substituted C₁₋₂₄ alkyl; —C(R³⁴)(R³⁵)COOR³⁶,—C(R³⁴)(R³⁵)C(O)H, —C(R³⁴)(R³⁵)C(O)R³⁷, —C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵)C(O)NR⁴¹R⁴², —C(R³⁴)(R³⁵)C(O)NR⁴¹OR⁴⁰, —C(O)R²⁵, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R³³ can form an optionally substitutedheterocyclic ring or is nil when W is halogen;R²¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₆cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ can form a polycyclic ring;R²¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²⁰ or together with R²² can form apolycyclic ring;R²² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²¹ or together with R² can form apolycyclic ring;R²³ is H, optionally substituted C₁₋₂ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²² can form a polycyclic ring;R²⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl;R²⁵ is OH, OR³⁰, NR²⁷R²⁸, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl,R²⁶ is H, optionally substituted C₃₋₈ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁷ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R²⁹ is H, optionally substituted C₁₋₂₄ alkyl, OR²⁶, —NR²⁷R²⁸, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl;R³⁰ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³³ is H, optionally substituted C₁₋₁₂ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl, optionally substituted C₃₋₈ cycloalkenyl, ortogether with R¹⁹ can form an optionally substituted heterocyclic ring;R³⁴ is H, optionally substituted C₁₋₁₂ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁵ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁶ is H, optionally substituted C₁₋₂₄alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³⁷ is optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R³⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R³⁹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈, cycloalkenyl;R⁴⁰ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl:R⁴¹ is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl;R⁴² is H, optionally substituted C₁₋₂₄ alkyl, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted heterocycle, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl; andx is 1 or 2.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising:subjecting a substrate represented by Formula (II)

together with cis-octen-1-ol in the presence of a stereoretentiveruthenium olefin metathesis catalyst represented by Formula (I) asdefined herein or in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V) as defined herein; andwherein:R^(v) is selected from

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<; comprisingsubjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I) as defined herein.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I) as defined herein.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (III)

wherein at least one carbon-carbon double bond has Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I) as defined herein.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I) as defined herein.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V) as defined herein.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (II)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V) as defined herein.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V) as defined herein.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V) as defined herein.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 9515, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprisingsubmitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I) as defined herein; andwherein R^(v) is

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprisingsubmitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V) as defined herein; andwherein R^(v) is

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at east one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; by submitting analcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I) as defined herein; andwherein R^(v) is

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(v) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprisingsubmitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V) as defined herein; andwherein R^(v) is selected from

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (II)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I) as defined herein; andwherein R^(v) is

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; by submitting analcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V) as defined herein; andwherein R^(v) is selected from

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented b Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 9/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I) as defined herein; andwherein R^(v) is

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 9/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented Formula (V) as defined herein; andwherein R^(v) is

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is selected from

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a WE-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (U)

wherein: R^(v) is selected from

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H. R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ isMe; R¹¹ is H; R¹² is Me; R¹³ is H; R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr, R²⁰ is H; R²¹ is H; R²² is H; R²³ is H;and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein R^(v) is selected from

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V), wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (I)

wherein: R^(v) is selected from

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V), wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; by submitting analcohol product of Formula (III),

wherein R^(v) is selected from

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I); wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H;R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰ is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H;R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰is H; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; by submitting analcohol product of Formula (III),

wherein R^(v) is selected from

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I); wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H;R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ is Me; R¹¹ is H; R¹² is Me; R¹³ is H;R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ isH; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 982, or 99/1, or >99/<1; by submitting analcohol product of Formula (III),

wherein R^(v) is selected from

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V); wherein W is O; X¹ isnitrate; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ isMe; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; by submitting analcohol product of Formula (III),

wherein R^(v) is selected from

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate or to oxidation in the presenceof pyridinium chlorochromate and sodium chlorite; wherein the alcoholproduct of Formula (III) is formed during the cross-metathesis reactionbetween a substrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V); wherein W is O; X¹ isnitrate; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ isH; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ isMe; R¹¹ is H; R¹² is Me; R¹³ is H; R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ is H;and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is i;R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ isMe; R¹¹ is H; R¹² is Me; R¹³ is H; R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ is H;and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising:subjecting a substrate represented by Formula (H)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V), wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V), wherein W is O; X¹ is nitrate; R¹ is F; R² is H; R³ is H;R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa Z-selective ruthenium olefin metathesis catalyst represented byFormula (V), wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H;R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising:subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reason in the presence of aZ-selective ruthenium olefin metathesis catalyst represented by Formula(V), wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H; R⁴ is H;R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr R²⁰ is H;R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,subjecting a substrate represented by Formula (I)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst representedFormula (I), wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ isMe; R¹¹ is H; R¹² is Me; R¹³ is H; R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ is H;and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising:subjecting a substrate represented by Formula (II)

wherein: R^(v) is

with cis-5-octen-1-ol to a cross-metathesis reaction in the presence ofa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I), wherein X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr, R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is J.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprisingsubmitting an alcohol product of Formula II,

wherein R^(v) is

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate; wherein the alcohol product ofFormula (III) is formed during the cross-metathesis reaction between asubstrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I); wherein: X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H;R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰ is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H;R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰is H; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein

R^(v) is

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate; wherein the alcohol product ofFormula (III) is formed during the cross-metathesis reaction between asubstrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I); wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is if; R⁴ is H; R⁵ is Me; R⁶ is H;R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ is Me; R¹¹ is H; R¹² is Me; R¹³ is H;R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ isH; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate; wherein the alcohol product ofFormula (III) is formed during the cross-metathesis reaction between asubstrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I): wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H;R⁷ is H; R⁸ is H; R⁹ is i-Pr, R¹⁰ is i-Pr, R¹¹ is H; R¹² is H; R¹³ is H;R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr, R²⁰is H; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivity95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; by submitting analcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate; wherein the alcohol product ofFormula (III) is formed during the cross-metathesis reaction between asubstrate represented by Formula (II)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I); wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H;R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ is Me; R¹¹ is H; R¹² is Me; R¹³ is H;R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ isH; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate; wherein the alcohol product ofFormula (III) is formed during the cross-metathesis reaction between asubstrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V); wherein W is O; X¹ isnitrate; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ isH; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of tetrapropylammonium perruthenate and4-methylmorpholine N-oxide monohydrate; wherein the alcohol product ofFormula (III) is formed during the cross-metathesis reaction between asubstrate represented by Formula (II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V); wherein: W is O; X¹ isnitrate; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ isMe; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²² isH; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula III wherein R^(v) is

to oxidation in the presence of pyridinium chlorochromate and sodiumchlorite; wherein the alcohol product of Formula (III) is formed duringthe cross-metathesis reaction between a substrate represented by Formula(II)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V); wherein W is O; X isnitrate; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr, R⁶ is H; R⁷ isH; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³is H; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV).

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of pyridinium chlorochromate and sodiumchlorite; wherein the alcohol product of Formula (I) is formed duringthe cross-metathesis reaction between a substrate represented by Formula(I)

and cis-octen-1-ol in the presence of a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V); wherein W is O; X¹ isnitrate; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H; R⁷ isMe; R⁸ is H; R⁹ is Me; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of pyridinium chlorochromate and sodiumchlorite; wherein the alcohol product of Formula (III) is formed duringthe cross-metathesis reaction between a substrate represented by Formula(III)

and cis-octen-1-ol in the presence of a stereoretentive ruthenium olefinmetathesis catalyst represented by Formula (I); wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H;R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰ is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H;R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰is H; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

In one embodiment, the invention provides a method for producing atleast one Δ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III), wherein R^(v) is

to oxidation in the presence of pyridinium chlorochromate and sodiumchlorite; wherein the alcohol product of Formula (III) is formed duringthe cross-metathesis reaction between a substrate represented by Formula(II)

and cis-octen-1-ol in the presence of a stereoselective ruthenium olefinmetathesis catalyst represented by Formula (I); wherein X is S; Y is S;Z is N; W is O; R¹ is H; R² is H; R³ is H; R⁴ is H; R⁵ is Me; R⁶ is H;R⁷ is Me; R⁸ is H; R⁹ is Me; R¹⁰ is Me; R¹¹ is H; R¹² is Me; R¹³ is H;R¹⁴ is Me; R¹⁵ is Cl; R¹⁶ is H; R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ isH; R²¹ is H; R²² is H; R²³ is H; and R²⁴ is H.

EXPERIMENTAL

In the following examples, efforts have been made to ensure accuracywith respect to numbers used (e.g., amounts, temperature, etc.) but someexperimental error and deviation should be accounted for. Unlessindicated otherwise, temperature is in degrees Celsius and pressure isat or near atmospheric. The examples are to be considered as not beinglimiting of the invention as described herein and are instead providedas representative examples of the catalyst compounds of the invention,of the methods that may be used in their preparation, and of the methodsof using the inventive catalysts.

Materials and Methods

Unless noted in the specific procedure, reactions were performed inflame-dried glassware under argon atmosphere. All metathesis reactionswere carried out under air-free conditions in dry glassware in a VacuumAtmospheres Glovebox filled with N₂. General solvents were purified bypassing through solvent purification columns. Commercially availablesubstrates were used as received. All solvents and substrates weresparged with Ar before bringing into the glovebox and filtered overbasic alumina (Brockmann I) prior to use. Reaction progress wasmonitored by thin-layer chromatography (TLC) using E. Merck silica gel60 F254 precoated plates (0.25 mm) and visualized by UV fluorescencequenching, potassium permanganate, or p-anisaldehyde staining. SilicycleSiliaFlash P60 Academic Silica gel (particle size 0.040-0.063 mm) wasused for flash chromatography. Analytical chiral HPLC was performed withan Agilent 1100 Series HPLC utilizing a Chiralcel OD-H column (4.6 mm×25cm) obtained from Daicel Chemical Industries, Ltd. with visualization at254 nm. Analytical SFC was performed with a Mettler SFC supercriticalCO₂ analytical chromatography system utilizing Chiralcel (IC) column(4.6 mm×25 cm) obtained from Daicel Chemical Industries, Ltd. withvisualization at 210 nm. GC conversion data was obtained using an HP-5capillary column with an Agilent 6850 FID gas chromatograph. ¹H and ¹³CNMR spectra were recorded on a Varian Inova 500 spectrometer (500 MHzand 126 MHz, respectively), a Bruker AV III HD spectrometer equippedwith a Prodigy liquid nitrogen temperature cryoprobe (400 MHz and 101MHz, respectively), or a Varian Mercury 300 spectrometer (300 MHz and 75MHz, respectively) and are reported in terms of chemical shift relativeto residual CHCl₃ (δ 7.26 and δ 77.16 ppm, respectively). Data for ¹HNMR spectra are reported as follows: chemical shift (6 ppm)(multiplicity, coupling constant (Hz), integration). Abbreviations areused as follows: s=singlet, bs=broad singlet, d=doublet, t=triplet,q=quartet, quint=quintet, m=complex multiplet. Infrared (IR) spectrawere recorded on a Perkin Elmer Paragon 1000 spectrometer using neatsamples on ATR diamond, and are reported in frequency of absorption(cm⁻¹). High-resolution mass spectra HRMS were acquired from the CaltechMass Spectral Facility using fast-atom bombardment (FAB⁺), electrosprayionization (IOF ES⁺) or electron impact (El⁺). Optical rotations weremeasured on a Jasco P-2000 polarimeter using a 100 mm path-length cellat 589 nm.

The following abbreviations are used herein:

RT or r.t. room temperatureCDCl₃ deuterated chloroformCHCl₃ chloroformC₆H₆ benzeneTHF tetrahydrofuranNaH₂PO₄.H₂O sodium dihydrogen phosphate monohydrateNaClO₂ sodium chloriteNMO.H₂O 4-methylmorpholine N-oxide monohydrateTPAP tetrapropylammonium perruthenateMeCN acetonitrileEt₂O diethyl etherNaHCO₃ sodium bicarbonater-BuOH tert-butylalcoholDCM/CH₂Cl₂ dichloromethaneDMAP 4-dimethylaminopyridineSiO₂ silicagel

Example 1 Preparation of alcohol 14

In a nitrogen-filled glovebox, cis-5-octen-1-ol (150 mg, 1.17 mmol, 8.0equiv) was dissolved in toluene (2 mL) in a 50 mL. Schienk flask, and asolution of catalyst Ru-4 (9.9 mg, 11.7 μmol, 1 mol %) in THF (0.7 mL)was added. The Schlenk flask was sealed and brought out of the glovebox,and then connected to high vacuum. The valve was gradually opened(Caution: open slowly and stir well to avoid splashing). After 15minutes stirring, the flask was refilled with argon and sealed, and wasbrought back into the glovebox. The residue was diluted with THE (0.5mL), and an aliquot was taken for GC analysis (conversion ofhomodimerization step was >98% by GC analysis). A solution of 11 [CAS2135628-52-1] (53 mg, 0.146 mmol, 1.0 equiv) in THF (0.5 mL) was addedinto the Schlenk flask and an additional portion of catalyst Ru-4 (6.2mg, 7.3 μmol, 5 mol %) solution in THF (0.3 mL) was added. The Schienkflask was sealed and brought out of glovebox. The reaction was stirredfor 24 h at 40° C. before a few drops of ethyl vinyl ether were added.The solvent was removed under reduced pressure. The residue was purifiedby flash chromatography (SiO₂, hexanes/EtOAc 2:1) to give 14 (60 mg,95%, >99:1 Z/E).

TLC (3:1 hexanes/EtOAc): Rf=0.23 (UV).

¹H NMR (400 MHz, CDCl₃): δ 7.50 (ddd, J=6.0, 2.6, 1.0 Hz, 1H), 6.59(ddt, J=8.3, 7.0, 1.3 Hz, 1H), 6.33 (dd, J=6.0, 1.8 Hz. 1H), 5.49 (dddt,J=8.6, 7.2, 5.5, 1.5 Hz, 1H), 5.35 (dtt, J=11.0, 8.4, 1.6 Hz, 1H), 3.84(quint, J=5.9 Hz, 1H), 3.63 (t, J=6.5 Hz, 2H), 3.46 (ddt, J=11.0, 4.2,2.2 Hz, 1H), 2.63 (dddd, J=13.8, 6.5, 4.2, 1.5 Hz, 1H), 2.50-2.34 (m,2H), 2.17 (dddd, 7=14.5, 9.4, 8.0, 1.3 Hz, 1H), 2.07-1.97 (m, 2H),1.60-1.51 (m, 2H), 1.47-1.34 (m, 6H), 1.32-1.19 (m, 5H), 0.95-0.81 (m,12H), 0.05 (s, 3H), 0.05 (s, 3H).

¹³C NMR (101 MHz, CDCl₃): δ 196.5, 161.8, 138.8, 135.0, 132.7, 132.5,125.4, 71.7, 62.9, 43.6, 37.5, 37.5, 32.5, 32.0, 30.7, 27.2, 26.0, 25.8,25.1, 22.8, 18.2, 14.2, −4.2, −4.5.

FTIR (ATR): 3443, 2956, 2928, 2856, 1703, 1652, 1580, 1472, 1360, 1251,1206, 1127, 1048, 1005, 975, 866, 834, 806, 773, 726, 664 cm⁻¹.

HRMS (TOF, ES⁺, m/z): calc'd for C₂₆H₄₇O₃Si [M+H]⁺ 435.3289, found:435.3298.

[α]^(D) ₂₃: +83.5° (c=1.0, CHCl₃).

Example 2 Preparation of Δ¹²-prostaglandin J₂ (1)

To a stirred solution of 14 (26 mg, 0.06 mmol, 1.0 equiv) in MeCN (0.3mL) was added NMO.H₂O (81 mg, 6 mmol, 10.0 equiv). Tetrapropylammoniumperruthenate (2.1 mg, 6 μmol, 0.1 equiv) was added until NMO.H₂O wasfully dissolved, and the reaction was stirred at 23° C. for 3 hours. Thesolution was diluted with Et₂O (5 mL), passed through a short pad ofsilica gel, concentrated and was subjected to the next reaction withoutfurther purification. The residue was dissolved in MeCN (1.0 mL) andcooled to 0° C. A solution of hydrofluoric acid

(48 wt. % in H₂O, 0.2 mL) In MeCN (0.4 mL) was added dropwisely. Thesolution was stirred in the same temperature for 30 min before saturatedNaHCO₃ solution (1.5 mL) and brine (1.5 mL) were added. The aqueousphase was extracted with EtOAc (5×5 mL). The combined organic phaseswere dried over magnesium sulfate, filtered and concentrated (not todryness). The residue was purified by flash chromatography (SiO₂,CH₂Cl₂/MeOH 20:1) to give 1 (18 mg, 89%over 2 steps) as a colorless liquid.

TLC (20:1 CH₂Cl₂/MeOH): Rf=0.14 (UV).

¹H NMR (500 MHz, CDCl₂): δ 7.57 (ddd, J=6.0, 2.6, 1.0 Hz, 1H), 6.58(ddt, J=8.4, 7.2, 1.3 Hz, 1H), 6.36 (dd, J=6.0, 1.8 Hz, 1H), 5.54-5.38(m, 2H), 3.86 (dtt, J=7.9, 6.4, 4.0 Hz, 1H), 3.47 (ddt, J=9.5, 4.0, 2.1Hz, 1H), 2.78-2.68 (m. 1H), 2.57 (dt, J=14.8, 6.8 Hz, 1H), 2.52-2.42 (m,1H), 2.40-2.33 (m, 2H), 2.20-2.02 (m, 3H), 1.77-1.64 (m, 2H), 1.61-1.41(m, 3H), 1.40-1.24 (m, 5H), 0.90 (t, J=6.8 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃): δ 196.6, 177.3, 162.0, 139.8, 135.0, 131.8,131.7, 126.2, 71.5, 43.9, 37.3, 36.7, 33.1, 31.9, 30.6, 26.6, 25.4,24.6, 22.8, 14.2.

FTIR (ATR): 3445, 2960, 2929, 2858, 1699, 1646, 1579, 1463, 1406, 1265,1237, 1135, 1084, 1033, 842, 810, 734, 702 cm⁻¹.

HRMS (TOF, ES⁺, m/z): calc'd for C₂₀H₃₁O₄[M+H]⁺ 335.2217, found:335.2223.

[α]^(D) ₂₃: +99.5° (c=0.2, CHCl₃).

Spectral data (¹H NMR, ¹³C NMR, HRMS matched with the published data:Acharya, H. P.; Kobayashi, Y. Highly Efficient Total Synthesis ofΔ¹²-PGJ₂, 15-Deoxy-Δ¹², —PGJ₂, and Their Analogues, Tetrahedron 2006,62, 3329-3343.

Example 3 Preparation of Alcohol 17

In a nitrogen-filled glovebox, cis-5-octen-1-ol (113 mg, 0.88 mmol, 8.0equiv) was dissolved in toluene (1 mL) in a 50 mL Schienk flask and asolution of catalyst Ru-4 (7.5 mg. 8.8 μmol, mol %) in THF (0.6 mL) wasadded. The Schlenk flask was sealed and brought out of the glovebox, andthen connected to high vacuum. The valve was gradually opened (Caution:open slowly and stir well to avoid splashing). After 15 minutesstirring, the flask was refilled with argon and sealed, and was broughtback into the glovebox. The residue was diluted with THF (0.5 mL), andan aliquot was taken for GC analysis (conversion of homodimerizationstep was >98% by GC analysis). A solution of 16 [CAS 2254448-24-1] (25mg, 0.11 mmol, 1.0 equiv) in THF (0.5 mL) was added into the Schienkflask and an additional portion of catalyst Ru-4 (4.6 mg, 5.5 μmol, 5mol %) solution in THE (0.2 mL) was added. The Schienk flask was sealedand brought out of glovebox. The reaction was stirred for 24 h at 40° C.before a few drops of ethyl vinyl ether were added. The solvent wasremoved under reduced pressure. The residue was purified by flashchromatography (SiO₂, hexanes/EtOAc 2:1) to give 17 (31 mg, 93%, >99:1Z/E, 87% ee by chiral HPLC analysis).

TLC (4:1 hexanes/EtOAc): Rf=0.2 (JV).

¹H NMR (400 MHz, CDCl₃) δ 7.48 (ddd, J=6.0, 2.6, 1.0 Hz, 1H), 6.95 (dt,J=11.0, 1.3 Hz, 1H), 6.35 (dd, J=6.0, 1.8 Hz, 1H), 6.34-6.19 (m, 2H),5.52-5.44 (m, 1H), 5.38-5.30 (m, 1H), 3.63 (t, J=6.5 Hz, 2H), 3.60-3.55(m, 1H), 2.60 (dddd, J=14.0, 6.2, 4.3, 1.4 Hz, 1H), 2.30 (dtd, J=14.4,8.6, 1.2 Hz, 1H), 2.25-2.17 (m, 2H), 2.01 (qd, J=7.3, 1.4 Hz, 2H),1.59-1.49 (m, 2H), 1.48-1.37 (m, 5H), 1.34-1.29 (m, 4H), 0.89 (t, J=7.0Hz, 3H).

¹³C NMR (101 MHz, CDCl₃): δ 197.6, 160.9, 147.0, 135.4, 135.3, 132.6,131.8, 125.8, 125.3, 62.9, 43.7, 33.6, 32.5, 31.5, 30.9, 28.6, 27.2,25.8, 22.6, 14.2.

FTIR (ATR): 3445, 2960, 2930, 2862, 1690, 1629, 1580, 1447, 1264, 1207,1054, 979, 732 cm⁻¹.

HRMS (TOF, ES⁺, m/z): calc'd for C₂₀H₃₁O₂[M+H]⁺ 303.2319, found:303.2320.

[α]^(D) ₂₃: +115.8° (c=0.5, CHCl₃).

HPLC Conditions: 10% IPA, 1.0 mL/min, Chiralcel OD-H column, λ=254 nm,tR (min): major=10.12, minor=13.57.

Example 4 Preparation of 15-deoxy-Δ^(12,14)-prostaglandin J₂ (2)

To a stirred solution of 17 (14 mg, 0.046 mmol, 1.0 equiv) in MeCN (0.5mL) was added NMO.H₂O (65 mg, 0.46 mmol, 10.0 equiv).Tetrapropylammonium perruthenate (1.7 mg. 4.6 μmol, 0.1 equiv) was addeduntil NMO.H₂O was fully dissolved, and the reaction was stirred at 23°C. for 3 hours. The reaction mixture was stirred for 3 hours and thesolvent was removed in vacuo. The residue was loaded onto a silica gelcolumn, flushed with CH₂Cl₂ then CH₂Cl₂/MeOH (20:1).15-deoxy-Δ^(12,14)-prostaglandin J₂ (2) was obtained as a colorless oil(10 mg, 68% yield).

TLC (100% EtOAc): Rf=0.70 (UV).

¹H NMR (400 MHz, CDCl₃): δ 7.47 (ddd, J=6.0, 2.6, 1.0 Hz, 1H), 6.95 (d.J=11.0 Hz, 1H), 6.38-6.35 (m, 1H), 6.33-6.20 (m, 2H), 5.50-5.33 (m, 2H),3.59 (ddd, J=8.4, 4.1, 2.2 Hz, 1H), 2.59 (m, 1H), 2.36-2.19 (m, 5H),2.05 (q, J=7.3 Hz, 2H), 1.68 (quint, J=7.5 Hz, 2H), 1.50-1.41 (m, 2H),1.34-1.28 (m. 4H), 0.90 (t, J=7.0 Hz, 3H).

¹³C NMR (101 MHz, CDCl₃): δ 197.6, 177.9, 160.8, 147.2, 135.5, 135.1,131.9, 131.5, 126.2, 125.8, 43.6, 33.6, 33.2, 31.6, 30.8, 28.6, 26.7,24.6, 22.6, 14.2.

FTIR (ATR): 2960, 2928, 2850, 1708, 1692, 1629, 1456, 1265, 1207, 978,734, 703 cm⁻¹.

HRMS (TOF, ES⁺, m/z): calc'd for C₂₀H₂₉O₃ [M+H]⁺ 317.2111, found:317.2127.

[α]^(D) ₂₃: +106.2° (c=0.2, CHCl₃).

Spectral data (¹H NMR, ¹³C NMR, HRMS) matched with the published data:

Acharya, H. P.; Kobayashi, Y. Highly Efficient Total Synthesis ofΔ12-PGJ₂, 15-Deoxy-Δ^(12,14)-PGJ₂, and Their Analogues. Tetrahedron2006, 62, 3329-3343.

Brummond, K. M.; Sill. P. C.; Chen, H. The First Total Synthesis of15-Deoxy-Δ^(12,14)-Prostaglandin J₂ and the Unambiguous Assignment ofthe C14 Stereochemistry. Org. Lett. 2004, 6, 149-152. Kim, N.-J.; Moon,H.; Park, T.; Yun, H.; Jung, J.-W.; Chang, D.-J.; Kim, D.-D.; Suh. Y.-G.Concise and Enantioselective Total Synthesis of15-Deoxy-Δ^(12,14)-Prostaglandin J₂ . J. Org. Chem. 2010, 75, 7458-7460.Egger, J.; Fischer, S.; Bretscher, P.; Freigang, S.; Kopf, M.; Carreira,E. M. Total Synthesis of Prostaglandin 15d-PGJ₂ and Investigation of ItsEffect on the Secretion of IL-6 and IL-12. Org. Lett. 2015, 17,4340-4343.

Example 5 Preparation of Alcohol 23 in the Presence of Ru-4

In a nitrogen-filled glovebox, cis-5-octen-1-ol (72 mg, 0.55 mmol, 6.7equiv) was dissolved in toluene (1 mL) in a 50 mL Schlenk flask and asolution of catalyst Ru-4 (4.7 mg, 5.6 μmol, 1 mol %) in THF (0.6 mL)was added. The Schlenk flask was sealed and brought out of the glovebox,and then connected to high vacuum. The valve was gradually opened(Caution: open slowly and stir well to avoid splashing). After 15minutes stirring, the flask was refilled with argon and sealed, and wasbrought back into the glovebox. The residue was diluted with 0.5 mL THF,and an aliquot was taken for GC analysis (conversion of homodimerizationstep was >98% by GC analysis). A solution of 22 [CAS 2254448-26-3] (30mg, 0.083 mmol, 1 equiv) in 0.5 mL THF was added into the Schlenk flaskand an additional 0.4 mL of catalyst solution with Ru-4 (2.9 mg, 3.5μmol, 5 mol %) was added. The Schienk flask was sealed and brought outof glovebox. The reaction was stirred for 12 h at 23° C. before a fewdrops of ethyl vinyl ether were added. The solvent was removed underreduced pressure. The residue was purified by flash chromatography(hexanes/EtOAc 10:1 to 2:1). 23 (16 mg. 44%) and 24 (8 mg, 31%) wasisolated as two products.

Compound 23:

TLC (2:1 hexanes/EtOAc): Rf=0.28 (UV).

¹H NMR (400 MHz, CDCl₃) δ 7.50 (ddd, J=6.0, 2.7, 1.0 Hz, 1H), 6.60 (ddt,8.2, 7.0, 1.3 Hz, 1H), 6.32 (dd, J=6.0, 1.8 Hz, 1H), 5.53-5.43 (m, 2H),5.41-5.31 (m. 2H), 3.89 (quint, J=6.1 Hz. 1H), 3.64 (t, J=6.5 Hz, 2H),3.45 (ddq, J=8.4, 4.3, 2.2 Hz, 1H). 2.68-2.55 (m, 1H), 2.43 (ddd, J=7.7,6.4, 2.3 Hz, 2H), 2.29-2.11 (m, 3H), 2.08-1.91 (m, 4H), 1.62-1.51 (m,2H), 1.48-1.36 (m, 2H), 0.94 (t, J=7.6 Hz, 3H), 0.88 (s, 9H), 0.06 (s,3H), 0.05 (s, 3H).

¹³C NMR (101 MHz, CDCl₃) δ 196.5, 161.8, 138.9, 135.0, 134.2, 132.7,132.5, 125.5, 124.4, 71.7, 62.9, 43.6, 37.0, 35.3, 32.5, 30.8, 27.2,26.0, 25.9, 20.9, 18.2, 14.3, −4.4, −4.4.

FTIR (ATR): 3429, 2956, 2928, 2856, 2361, 2327, 1702, 1652, 1580, 1472,1360, 1251, 1213, 1066, 1005, 968, 834, 807, 774, 721, 668 cm⁻¹.

HRMS (FAB⁺, m/z): calculated for C₂₆H₄₅O₃Si [M+H]⁺433.3132. found:433.3121.

[α]^(D) ₂₃: +136.3° (c=1.0, C₆H₆).

Compound 24:

TLC (2:1 hexanes/EtOAc): Rf=0.6 (UV).

¹H NMR (400 MHz, CDCl₃): δ 7.43 (ddd, J=5.9, 2.8, 1.0 Hz, 1H), 6.80(ddt, J=10.8, 8.8, 1.3 Hz, 1H), 6.31 (dd, J=5.9, 1.7 Hz, 1H), 5.76 (q,J=9.1 Hz. 1H), 5.61 (dddd, J=11.9, 10.7, 5.2, 1.2 Hz, 1H). 4.08-4.02 (m,1H), 3.27 (d, 9.6 Hz, 1H), 2.38 (dd, J=9.5, 3.0 Hz, 210, 2.24 (q, J=11.6Hz, 2H), 2.17-1.95 (m. 2H), 0.91 (s. 9H), 0.11 (s, 3H), 0.08 (s, 3H).

¹³C NMR (101 MHz, CDCl₃): δ 196.4, 162.3, 141.3, 134.0, 132.4, 130.6,129.6, 73.1, 44.2, 34.7, 34.5, 32.6, 26.0, 18.3, −4.6, −4.7.

FTIR (ATR): 2952, 2926, 2886, 2855, 2359, 2339, 1705, 1654, 1586, 1471,1369, 1251, 1190, 1077, 1039, 997, 980, 938, 855, 835, 808, 790, 774,727.668 cm⁻¹.

HRMS (FAB⁺, m/z): calculated for C₁₈H₂₉O₂Si [M+H]⁺305.1931, found:305.1942.

[α]^(D) ₂₃: −27.8° (c=0.8, CHCl₃)

Example 6 Preparation of Alcohol 23 in the Presence of Ru-2

In a nitrogen-filled glovebox, 22 (64 mg, 0.18 mmol, 1.0 equiv) and5-hexen-1-ol (142 mg, 1.42 mmol, 8.0 equiv) were weighed into a 4 mLvial. THF (0.3 mL) was added to dissolve the mixture. Catalyst Ru-2 (24mg, 20 mol %) was dissolved in THF (0.4 ml) and 0.1 mL of this catalystsolution was transferred into the vial. The vial was sealed with a 14/20septum and brought out of the glovebox. The reaction was stirred at 40°C. with a stream of argon (saturated with anhydrous THF) bubblingthrough a needle. A portion of the catalyst solution (0.1 mL) was addedinto the vial in each 1 hour. After all the catalyst was added, thereaction mixture was continued to stir for 4 h with argon bubbling. Afew drops of ethyl vinyl ether were added, and the reaction mixture wasconcentrated in vacuo. The residue was purified by column chromatography(SiO₂, hexanes/EtOAc 2:1) to afford 23 (40 mg, 52%) as a colorlessliquid. Compound 26 was the proposed by-product (molar ratio of 23:26was 32:1 as determined by crude NMR analysis).

Compound 23: Characterization data were in agreement with previouslyobtained data.

Compound 26: Characterization data not available due to the difficultyin separation, mass data was obtained by LC-MS (TOF, ES⁺, m/z):calculated for C₂₄H₄₁O₃Si [M+H]⁺ 405.2819, found: 405.2801.

Example 7 Preparation of Δ¹²-Prostaglandin J₃ (3)

To a stirred solution of 23 (21.6 mg, 0.05 mmol, 1.0 equiv) in MeCN (0.5mL) was added NMO.H₂O (67.5 mg, 0.5 mmol, 10.0 equiv).Tetrapropylammonium perruthenate (1.8 mg, 5 μmol, 0.1 equiv) was addeduntil NMO.H₂O was fully dissolved, and the reaction was stirred at 23°C. for 3 hours. The solution was diluted with Et₂O (5 mL), passedthrough a short pad of silica gel, concentrated and was subjected to thenext reaction without further purification.

The residue was dissolved in MeCN (1.0 mL) and cooled to 0° C. Asolution of hydrofluoric acid (48 wt. % in H₂O, 0.2 mL) in MeCN (0.4 mL)was added dropwisely. The solution was stirred in the same temperaturefor 30 min before saturated NaHCO₃ solution (1.5 mL) and brine (1.5 mL)were added. The aqueous phase was extracted with EtOAc (5×5 mL). Thecombined organic phase was dried over magnesium sulfate, filtered andconcentrated (not to dryness). The residue was purified by flashchromatography (SiO₂, CH₂Cl₂/MeOH 20:1) and through BiotageR SNAP UltraC₁₈ column (H₂O/MeOH) to give 3 (10 mg, 60% over 2 steps) as a colorlessliquid.

TLC (100% EtOAc): Rf=0.55 (UV).

¹H NMR (400 MHz, CDCl₃): δ 7.58 (ddd, J=6.0, 2.6, 1.0 Hz, 1H), 6.57(ddt, J=8.4, 7.0, 1.2 Hz, 1H), 6.36 (dd, J=6.0, 1.8 Hz, 1H), 5.69-5.60(m, 1H), 5.60-5.45 (m, 2H), 5.45-5.35 (m, 1H), 3.91 (quint, J=6.8 Hz,1H), 3.50-3.44 (m, 1H), 2.75 (ddd, J=13.9, 6.9, 4.4 Hz, 1H), 2.68-2.58(m. 1H), 2.49 (ddd, J=15.2, 8.4, 7.0 Hz, 1H), 2.36 (t, J=6.8 Hz, 2H),2.33-2.28 (m, 2H), 2.20-1.98 (m. 5H), 1.68 (quint, J=7.0 Hz, 2H), 0.96(t, J=7.5 Hz, 3H).

¹³C NMR (101 MHz, CDCl₃): δ 196.4, 175.8, 161.8, 139.9, 136.4, 135.1,131.7, 131.2, 126.3, 123.6, 71.1, 44.0, 36.3, 34.5, 32.9, 30.7, 26.6,24.7, 20.9, 14.4.

FTIR (ATR): 3449, 3010, 2956, 2919, 2850, 1728, 1703, 1650, 1579, 1455,1375, 1222, 1182, 1046, 959, 838, 809, 721 cm⁻¹.

HRMS (FAB⁺, m/z): calc'd for C₂₀H₂₉O₄ [M+H]⁺ 333.2060, found: 333.2060.

[α]^(D) ₂₃: +122.6° (c=0.5, C₆H₆).

Spectral data (¹H NMR, ¹³C NMR, HRMS) matched with the published data.6Comparisons of ¹H NMR data of natural and synthetic Δ¹²-prostaglandin J₃(3) are listed in Table S2 of J. Am. Chem. Soc.,

Example 8 Preparation of Alcohol 29 in the Presence of Ru-4

In a nitrogen-filled glovebox, cis-5-octen-1-ol (205 mg, 1.6 mmol. 8.0equiv) was dissolved in toluene (I mL) in a 50 mL Schienk flask and asolution of catalyst Ru-4 (13.6 mg, 16 μmol, 1 mol %) in THF (0.6 mL)was added. The Schlenk flask was sealed and brought out of the glovebox,and then connected to high vacuum. The valve was gradually opened(Caution: open slowly and stir well to avoid splashing). After 15minutes stirring, the flask was refilled with argon and sealed, and wasbrought back into the glovebox. The residue was diluted with 0.5 mL THF,and an aliquot was taken for GC analysis (conversion of homodimerizationstep was >98% by GC analysis). A solution of 28 [CAS 2254448-29-6] (46mg, 0.2 mmol, 1.0 equiv) in 0.5 mL THF was added into the Schlenk flaskand an additional 0.4 mL of catalyst solution with Ru-4 (8.5 mg, 10μmol, 5 mol %) was added. The Schienk flask was sealed and brought outof glovebox. The reaction was stirred for 12 h at 23° C. before a fewdrops of ethyl vinyl ether were added. The solvent was removed underreduced pressure. The residue was purified by column chromatography(SiO₂, hexanes/EtOAc 2:1). Compounds 29 (22 mg, 36%) and 30 wereseparated as a mixture (28 mg, molar ratio of 29:30 was 3:1 asdetermined by crude NMR analysis).

Compound 29: Characterization data not available due to the difficultyin separation.

Mass data was obtained by LC-MS (TOF. ES⁺, m/z): calc'd for C₂₀H₂₉O₂[M+H]⁺ 301.2162, found: 301.2080.

Compound 30: Characterization data not available due to the difficultyin separation, mass data was obtained by LC-MS (TOF, ES⁺, m/z):calculated for C₁₈H₂₅O₂ [M+H]⁺ 273.1849, found: 273.1759.

Example 9 Preparation of Alcohol 29 in the Presence of Ru-2

In a nitrogen-filled glovebox, 28 (23 mg, 0.1 mmol, 1.0 equiv) and5-hexen-1-ol (80 mg, 0.8 mmol, 8.0 equiv) were weighed into a 4 mL vial.THF (0.1 mL) was added to dissolve the mixture. Catalyst Ru-2 (13.6 mg,20 mol %) was dissolved in THF (0.4 mL) and 0.1 mL of this catalystsolution was transferred into the vial. The vial was sealed with a 14/20septum and brought out of the glovebox. The reaction was stirred at 40°C. with a stream of argon (saturated with anhydrous THF) bubblingthrough a needle. A portion of the catalyst solution (0.1 mL) was addedinto the vial in each 1 hour. After all the catalyst was added, thereaction mixture was continued to stir for 2 h with argon bubbling. Afew drops of ethyl vinyl ether were added, and the reaction mixture wasconcentrated in vacuo. The residue was purified by column chromatography(SiO₂, hexanes/EtOAc 2:1). Compounds 29 (9.2 mg, 31%) and 30 wereseparated as a mixture (12 mg, molar ratio of 29:30 was 3:1 asdetermined by crude NMR analysis).

Compound 29: Characterization data not available due to the difficultyin separation. Mass data was obtained by LC-MS (TOF, ES⁺, m/z): calc'dfor C₁₈H₂₅O₂[M+H]⁺ 273.1849, found: 273.1855.

Example 10 Preparation of 15-deoxy-Δ¹²⁴-prostaglandin J₃ (4) from 29

Pyridinium chlorochromate (22 mg, 0.1 mmol, 3.0 equiv) was added to asolution of 29 (mixed with by-product 30) (10 mg, 0.033 mmol, 1.0 equiv)in CH₂Cl₂ (0.5 mL) at 23° C. The reaction was monitored by TLC and wasdiluted with Et₂O (3 mL) after stirring for 3 h. The resulting solutionwas filtered through a short pad of silica gel and was subjected to thenext step without further purification. The residue was dissolved int-BuOH (0.5 mL) at 23° C., and 2-methyl-2-butene (35 μL, 0.33 mmol, 10equiv), a solution of NaH₂PO₄H₂O (6.9 mg, 0.05 mmol, 1.5 equiv) in H₂O(0.12 mL) and a solution of NaClO₂ (80%, 5.6 mg, 0.05 mmol, 1.5 equiv)in H₂O (0.12 ml) was added sequentially. After stirring at 23° C. for 30minutes, the reaction mixture was diluted with a solution of NaH₂PO₄.H₂O(108 mg) in H₂O (2 mL) and extracted with EtOAc (5×5 mL). The combinedorganic extracts were dried over anhydrous magnesium sulfate, filtered,and concentrated under reduced pressure. Flash column chromatography(SiO₂, CH₂Cl₂/MeOH 20:1) and purification through BiotageR SNAP UltraC18 column (H₂O/MeOH) afforded pure compound 4 (4 mg, 0.013 mmol, 12%yield from 28) as a colorless oil.

TLC (10:1 CH₂Cl₂/MeOH): Rf=0.44 (UV).

¹H NMR (500 MHz, CDCl₃): δ 7.48 (ddd, J=6.1, 2.6, 1.0 Hz, 1H), 6.96 (d,J=11.5 Hz, 1H), 6.42-6.31 (m, 2H), 6.22 (dt, J=14.9, 6.3 Hz, 1H),5.57-5.51 (m, 1H), 5.50-5.43 (m, 1H), 5.37 (dtt, J=10.1, 6.8, 1.7 Hz,2H), 3.64-3.55 (m, 1H), 2.98 (t, J=6.8 Hz, 2H), 2.60 (dt, J=12.3, 5.9Hz, 1H). 2.43-2.25 (m, 3H), 2.12-2.00 (m, 4H), 1.69 (quint, J=7.4 Hz,2H), 0.99 (t, J=7.5 Hz, 3H).

¹³C NMR (101 MHz, CDCl₃): δ 197.6, 176.6, 160.9, 144.5, 135.5, 135.5,134.2, 131.6, 131.5, 126.1, 125.8, 124.6, 43.6, 33.0, 31.2, 30.9, 26.7,24.6, 20.7, 14.3.

FTIR (ATR): 3010, 2960, 2926, 2874, 2854, 1710, 1693, 1626, 1578, 1512,1455, 1208, 1154, 1087, 1024, 977, 817, 728 cm⁻¹.

HRMS (FAB+, m/z): calc'd for C₂₀H₂₇O₃ [M+H]⁺315.1955, found: 315.1968.

[α]^(D) ₂₃: +129.6° (c=0.07, C₆H₆).

Spectral data (¹H NMR, ¹³C NMR, HRMS) matched with the published data:

Nicolaou, K. C.; Pulukuri, K. K.; Rigol, S.; Heretsch. P.; Yu, R.;Grove, C. I.; Hale, C. R. H.; ElMarrouni, A.; Fetz, V.; Bronstrup, M.;Aujay M.; Sandoval J.; Gavrilyuk J. Synthesis and BiologicalInvestigation of Δ¹²-Prostaglandin J₃ (Δ¹²-PGJ₃) Analogues and RelatedCompounds. J. Am. Chem. Soc. 2016, 138, 6550-6560.

1.-10. (canceled)
 11. A method for producing at least oneΔ¹²-Prostaglandin J product represented by Formula (IV),

wherein: R^(z) is selected from

and wherein at least one carbon-carbon double bond has a Z/E-selectivityof 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1; comprising,submitting an alcohol product of Formula (III)

to oxidation conditions; wherein the alcohol product of Formula (III) isformed during the cross-metathesis reaction between a substraterepresented by Formula (II)

and cis-octen-1-ol in the presence of a ruthenium olefin metathesiscatalyst; and wherein R^(v) is selected from


12. The method according to claim 11, wherein the ruthenium catalyst isa stereoretentive ruthenium olefin metathesis catalyst represented byFormula (I) is

X is O or S; Y is O or S; Z is N or CR³²; W is O, halogen, NR³³ or S; R¹is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R² can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring; R² isH, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R¹ can form a spiro compound ortogether with R³ or together with R⁴ can form a polycyclic ring; R³ isH, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl or together with R² or together with R¹ can form apolycyclic ring or together with R⁴ can form a spiro compound; R⁴ is H,optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R³ can form a spiro compound ortogether with R² or together with R¹ can form a polycyclic ring; R⁵ isH, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ can form an optionallysubstituted polycyclic ring; R⁶ is H, optionally substituted C₁₋₂₄alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄aryl, optionally substituted C₃₋₈ cycloalkenyl, or together with R⁵ ortogether with R⁷ can form an optionally substituted polycyclic ring; R⁷is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁶ or together with R⁸ can form anoptionally substituted polycyclic ring; R⁸ is H, optionally substitutedC₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃,—S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₅₋₂₄ aryl, optionally substituted C₃₋₈ cycloalkenyl, ortogether with R⁷ or together with R⁹ can form an optionally substitutedpolycyclic ring; R⁹ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl, or together with R⁸ can forman optionally substituted polycyclic ring; R¹⁰ is H, optionallysubstituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R¹¹ can form an optionally substitutedpolycyclic ring; R¹¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R¹⁰ ortogether with R¹² can form an optionally substituted polycyclic ring;R¹² is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶,CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹¹ or together with R¹³ can form anoptionally substituted polycyclic ring; R¹³ is H, optionally substitutedC₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃,—S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₅₋₂₄ aryl, optionally substituted C₃₋₈ cycloalkenyl, ortogether with R¹⁴ or together with R¹² can form an optionallysubstituted polycyclic ring; R¹⁴ is H, optionally substituted C₁₋₂₄alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄aryl, optionally substituted C₃₋₈ cycloalkenyl, or together with R¹³ canform a polycyclic ring; R¹⁵ is H, optionally substituted C₁₋₂₄ alkyl,halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄aryl or optionally substituted C₃₋₈ cycloalkenyl, or together with R¹⁶can form an optionally substituted polycyclic ring; R¹⁶ is H, optionallysubstituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl, or together with R¹⁵ or together with R¹⁷ can form anoptionally substituted polycyclic ring; R¹⁷ is H, optionally substitutedC₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃,—S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl, ortogether with R¹⁸ or together with R¹⁶ can form an optionallysubstituted polycyclic ring; R¹⁸ is H, optionally substituted C₁₋₂₄alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹,—P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄aryl or optionally substituted C₃₋₈ cycloalkenyl, or together with R¹⁷can form an optionally substituted polycyclic ring; R¹⁹ is H, optionallysubstituted C₁₋₂₄ alkyl, —C(R³⁴)(R³⁵)COOR³⁶, —C(R³⁴)(R³⁵)C(O)H,—C(R³⁴)(R³⁵)C(O)R³⁷, —C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰),—C(R³⁴)(R³⁵)C(O)NR⁴¹R⁴², —C(R³⁴)(R³⁵)C(O)NR⁴⁰R⁴¹, —C(O)R²⁵, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R³³ can form an optionally substitutedheterocyclic ring or is nil when W is halogen; R²⁰ is H, optionallysubstituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²¹ can form a polycyclic ring; R²¹ is H,optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl or together with R²⁰ or together with R²² can form apolycyclic ring; R²² is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R²¹ ortogether with R²³ can form a polycyclic ring; R²³ is H, optionallysubstituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²² can form a polycyclic ring; R²⁴ is H,optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁵ is OH, OR³⁰, NR²⁷R²⁸, optionally substitutedC₁₋₂₄ alkyl, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted heterocycle, optionally substituted C₅₋₂₄ aryl or optionallysubstituted C₃₋₈ cycloalkenyl, R²⁶ is H, optionally substituted C₁₋₂₄alkyl, optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁷ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁸ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R²⁹ is H, optionally substituted C₁₋₂₄ alkyl, OR²⁶,—NR²⁷R²⁸, optionally substituted heterocycle, optionally substitutedC₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl or optionallysubstituted C₃₋₈ cycloalkenyl; R³⁰ is optionally substituted C₁₋₂₄alkyl, optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³¹ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³² is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³³ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R¹⁹ can form an optionallysubstituted heterocyclic ring; R³⁴ is H, optionally substituted C₁₋₂₄alkyl, optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁵ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁶ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁷ is optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁹ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴⁰ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴¹ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴² is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; and x is 1 or
 2. 13. The method according to claim 11,wherein the ruthenium catalyst is a Z-selective ruthenium olefinmetathesis catalyst represented by Formula (V) is

wherein: W is O, halogen, NR³³ or S; X¹ is hydrogen, halide, nitrate,optionally substituted C₁-C₂₀ alkyl, optionally substituted C₅-C₂₄ aryl,optionally substituted C₁-C₂₀ alkoxy, optionally substituted C₁-C₂₀alkylcarboxylate, optionally substituted C₅-C₂₄ aryloxy, optionallysubstituted C₂-C₂₀ alkoxycarbonyl, optionally substituted C₆-C₂₄aryloxycarbonyl, optionally substituted C₆-C₂₄ arylcarboxylate,optionally substituted C₂-C₂₄ acyl, optionally substituted C₂-C₂₄acyloxy, optionally substituted C₁-C₂₀ alkylsulfonato, optionallysubstituted C₅-C₂₄ arylsulfonato, optionally substituted C₁-C₂₀alkylsulfanyl, optionally substituted C₅-C₂₄ arylsulfanyl, optionallysubstituted C₁-C₂₀ alkylsulfinyl, or optionally substituted C₅-C₂₄arylsulfinyl; R¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl, or together with R² can form aspiro compound or together with R³ or together with R⁴ can form apolycyclic ring; R² is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R¹ can form aspiro compound or together with R³ or together with R⁴ can form apolycyclic ring; R³ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl oroptionally substituted C₃₋₈ cycloalkenyl or together with R² or togetherwith R¹ can form a polycyclic ring or together with R⁴ can form a spirocompound; R⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl, or together with R³ can form aspiro compound or together with R² or together with R¹ can form apolycyclic ring; R⁵ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl, or together with R⁶ can forman optionally substituted polycyclic ring; R⁶ is H, optionallysubstituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R⁵ or together with R⁷ can form anoptionally substituted polycyclic ring; R⁷ is H, optionally substitutedC₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃,—S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionally substitutedheterocycle, optionally substituted C₃₋₈ cycloalkyl, optionallysubstituted C₅₋₂₄ aryl optionally substituted C₃₋₈ cycloalkenyl, ortogether with R⁶ or together with R⁸ can form an optionally substitutedpolycyclic ring; R⁸ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl, or together with R⁷ ortogether with R⁹ can form an optionally substituted polycyclic ring; R⁹is H, optionally substituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN,—NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹,optionally substituted heterocycle, optionally substituted C₃₋₈cycloalkyl, optionally substituted C₅₋₂₄ aryl, optionally substitutedC₃₋₈ cycloalkenyl, or together with R⁸ can form an optionallysubstituted polycyclic ring; R¹⁹ is H, optionally substituted C₁₋₂₄alkyl, —C(R³⁴)(R³⁵)COOR³⁶, —C(R³⁴)(R³⁵)C(O)H, —C(R³⁴)(R³⁵)C(O)R³⁷,—C(R³⁴)(R³⁵)CR³⁸(OR³⁹)(OR⁴⁰), —C(R³⁴)(R³⁵)C(O)NR⁴¹R⁴²,—C(R³⁴)(R³⁵)C(O)NR⁴¹OR⁴⁰, —C(O)R²⁵, optionally substituted heterocycle,optionally substituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄aryl, optionally substituted C₃₋₈ cycloalkenyl, or together with R³³ canform an optionally substituted heterocyclic ring or is nil when W ishalogen; R²⁰ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R²¹ can form apolycyclic ring; R²¹ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R²⁰ ortogether with R²² can form a polycyclic ring; R²² is H, optionallysubstituted C₁₋₂₄ alkyl, halogen, —C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂,—CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂, —OP(O)(OH)₂, —SR³¹, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl or together with R²¹ or together with R²³ can form apolycyclic ring; R²³ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl,optionally substituted C₃₋₈ cycloalkenyl or together with R²² can form apolycyclic ring; R²⁴ is H, optionally substituted C₁₋₂₄ alkyl, halogen,—C(O)R²⁵, —OR²⁶, CN, —NR²⁷R²⁸, NO₂, —CF₃, —S(O)_(x)R²⁹, —P(O)(OH)₂,—OP(O)(OH)₂, —SR³¹, optionally substituted heterocycle, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted C₅₋₂₄ aryl oroptionally substituted C₃₋₈ cycloalkenyl; R²⁵ is OH, OR³⁰, NR²⁷R²⁸,optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl, R²⁶ is H,optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁷ is H,optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁸ is H,optionally substituted C₁₋₂₄ alkyl, optionally substituted C₃₋₈cycloalkyl, optionally substituted heterocycle, optionally substitutedC₅₋₂₄ aryl or optionally substituted C₃₋₈ cycloalkenyl; R²⁹ is H,optionally substituted C₁₋₂₄ alkyl, OR²⁶, —NR²⁷R²⁸, optionallysubstituted heterocycle, optionally substituted C₃₋₈ cycloalkyl,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁰ is optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³¹ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³² is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³³ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl, optionally substituted C₃₋₈cycloalkenyl, or together with R¹⁹ can form an optionally substitutedheterocyclic ring; R³⁴ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁵ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁶ is H, optionally substituted C₁₋₂₄ alkyl,optionally substituted C₃₋₈ cycloalkyl, optionally substitutedheterocycle, optionally substituted C₅₋₂₄ aryl or optionally substitutedC₃₋₈ cycloalkenyl; R³⁷ is optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁸ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R³⁹ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴⁰ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴¹ is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; R⁴² is H, optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₃₋₈ cycloalkyl, optionally substituted heterocycle,optionally substituted C₅₋₂₄ aryl or optionally substituted C₃₋₈cycloalkenyl; and x is 1 or
 2. 14. The method according to claim 11,wherein the oxidation takes place in the presence of tetrapropylammoniumperruthenate and 4-methylmorpholine N-oxide monohydrate.
 15. The methodaccording to claim 11, wherein the oxidation takes place in the presenceof pyridinium chlorochromate and sodium chlorite.
 16. The methodaccording to claim 14, wherein R^(z) is

R^(v) is

and the ruthenium catalyst is a stereoretentive catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.
 17. The method according to claim 14, wherein R^(z) is

R^(v) is

and the ruthenium catalyst is a Z-selective catalyst represented byFormula (V) wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H; R⁴is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.
 18. The methodaccording to claim 15, wherein R^(z) is

R^(v) is

and the ruthenium catalyst is a stereoretentive catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.
 19. The method according to claim 15, wherein R^(z) is

R^(v) is

and the ruthenium catalyst is a Z-selective catalyst represented byFormula (V) wherein W is O; X¹ is nitrate; R¹ is H; R² is H; R³ is H; R⁴is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁹ is i-Pr;R²⁰ is H; R²¹ is H; R²² is H; R²³ is H; R²⁴ is H.
 20. The methodaccording to claim 15, wherein R^(z) is

R^(v) is

and the ruthenium catalyst is a stereoretentive catalyst represented byFormula (I) wherein: X is S; Y is S; Z is N; W is O; R¹ is H; R² is H;R³ is H; R⁴ is H; R⁵ is i-Pr; R⁶ is H; R⁷ is H; R⁸ is H; R⁹ is i-Pr; R¹⁰is i-Pr; R¹¹ is H; R¹² is H; R¹³ is H; R¹⁴ is i-Pr; R¹⁵ is Cl; R¹⁶ is H;R¹⁷ is H; R¹⁸ is Cl; R¹⁹ is i-Pr; R²⁰ is H; R²¹ is H; R²² is H; R²³ isH; and R²⁴ is H.